Effect of captopril on serum TNF-α level in acute lung injury rats induced by HCL

Objective:To observe the effect of captopril on the tumor necrosis factor-α(TNF- α) level and arterial blood gases in acute lung injury(All) induced by HCL in rats,and to analyze its protective mechanism.Methods:Fifty Wistar rats were selected and randomly divided into three groups,with 20 rats in Group Ⅰ and Ⅱ,respectively and 10 animals in Group Ⅲ.ALI model was constructed by intratracheal injection of diluted hydrochloric acid(pH=1.25.1.2 mL/kg).Group Ⅰrats received not any treatment after construction of AM model.Group Ⅱ rats were treated with captopril(5 mg/kg,i.p.) 5 min after induction of ALI.Group Ⅲ served as normal control without any treatment.Ninety minutes after construction of ALI model,all the rats were sacrificed.Blood was withdrawn for detection of TNF- α level and arterial blood gases index.And lung tissue slices of the three groups were prepared for observation of pathologic histology changes.Results:TNF- α level in serum of Group Ⅰ and Ⅱ rats was significantly higher than that in Group Ⅲ(P0.05),while TNF- α level in serum of Group Ⅱ was significantly lower in Group Ⅰ(P0.05).PaCO_2 level was significantly higher(P0.05),while PaO_2 was significantly lower(P0.05) in Group Ⅰ and Ⅱ rats than those in Group Ⅲ.PaCO_2 was significantly lower(P0.05) and PaO_2 was significantly higher(P0.05) in Group Ⅱ than those in Group Ⅰ.Histological observation showed diffuse congestion and severe edema of luug tissue,obvious thickening and structure damage of alveolar walls and a large amount of neutrophil infiltration in Group Ⅰ rats.Group Ⅱ rats showed mild edema of lung tissue;only a small portion of alveolar walls showed thickening and only a few of neutrophil infiltration could be observed.The degree of injury was remarkably slighter than that of Group Ⅰ rats.Group Ⅲ rats showed clear lung tissue structure and normal morphology:alveolar walls were uniform and the margin was smooth and few neutrophil could be observed.Conclusions:Captopril can significantly reduce serum TNF- α level,elevate PaO_2 and reduce PaCO_2 in rats with ALI.It has a protective effect on ALI rats.     

Preventive effects of sevoflurane treatment on lung inflammation in rats

ObjectiveTo observe the effects of sevoflurane treatment on lung inflammation in rats with lipopoIysaccharide-induced acute lung injury (ALI).MethodsThe rat model of ALI was established by intratracheal instillation of lipopolysaccharide (LPS). 45 infantile SD rats [body weight (272±15) g] were randomly divided into 3 groups (n=15): control group, LPS group, sevoflurane group. NS (1 mL/kg) was instillated in rats' airways of control group; LPS (5 mg/kg) was instillated in rats' airways of LPS group. Sevoflurane group rats received sevoflurane (2.4%) inhalation for a hour after LPS was instillated in rats' airways. Six hours after NS or LPS instillation, all rats were exsanguinated. Lung tissues were examined by HE staining. Expressions of TNF-α and ICAM1 mRNA were detected by semiquantitative RT-PCR techniques. The protein level of TNF-α and ICAM1 were assessed by western blot techniques.ResultsIn LPS group the permeability of lung tissues increased, organizational structure severely damaged and the alveolar wall tumed thick, with interstitial edema and Europhiles infiltrated increasingly. The LPS group had higher mRNA expressions of TNF-α and ICAM1 than control group and sevoflurane group (P<0.05), and LPS group had higher protein level of TNF-α and ICAM1 than control group and sevoflurane group (P<0.05).ConclusionsSevoflurane treatment can attenuate lung inflammation in rats with lipopolysaccharide-induced acute lung injury.     

Expression and significance of MMP-9 and MDM2 in the oncogenesis of lung cancer in rats

Objective:To observe the expression of matrix metalloproteinase-9(MMP-9)and mouse double minute 2 homolog(MDM2)in the oncogenesis of lung cancer in rats and to explore their clinical value.Methods:A total of 140 rats were selected,of which 20 were selected randomly as the control group;and the remaining 120 as the observation group.The observation group was injected with benzopyrene to establish diseases model such as tissue proliferation,abnormal proliferation and lung cancer.Delected the MMP-9 levels of lung tissue by enzyme-linked assay,detected the MDM2 levels of lung tissue by immunochemistry assay.Results:The MMP-9 and MDM2 expression of the lung cancer group and the abnormal proliferation group were significantly higher than that in the tissue proliferation group and the control group,the difference was significant(P0.05).And the MDM2 expression of the tissue proliferation group was significantly higher than that in the control group,the difference was significant(P0.05).There was no significant difference in the MMP-9 expression between the tissue proliferation group and the control group(P0.05).The MDM2 and MMP-9 expression were increased in turn in the small cell carcinoma,squamous cell carcinoma and adenocarcinoma,the difference was statistically significant(P0.05).The MMP-9 and MDM2 expressions of stageⅢand stageⅣlung cancer tissue in rats were significant higher than that during stageⅠand stageⅡ,the difference was significant(P0.05).There was no significantly different in the MMP-9 and MDM2 expressions between stageⅢand stageⅣ(P0.05),and there is no significant difference of the MMP-9and MDM2 expressions between stageⅠand stageⅡ(P0.05).Conclusions:The expression of MMP-9 and MDM2 in lung tissue was associated with lung disease and lung cancer,both of them may be involved in the development and metastasis of lung cancer.Combined detection can be used as therapy and prognostic indicators for lung cancer.     

Effect and mechanism of salvianolic acid B on the myocardial ischemiareperfusion injury in rats

Objective:To investigate the effect of salvianolic acid B on rats with myocardial ischemiareperfusion injury.Methods:SD rats were randomly divided into five groups(n=10 in each group):A sham operation group,B ischemic reperfusion group model group,C low dose salvianolic acid B group,D median dose salvianolic acid B group,E high dose salvianolic acid B group.One hour after establishment of the myocardial ischemia-reperfusion model,the concentration and the apoptotic index of the plasma level of myocardial enzymes(CTnⅠ,CKMB),SOD,MDA,NO,ET were,measured.Heart tissues were obtained and micro-structural changes were observed.Results:Compared the model group,the plasma CTnⅠ,CK-MB,MDA and ET contents were significantly increased,NO,T-SOD contents were decreased in the treatment group(group C,D,and E)(P0.05);compared with group E,the plasma CTnⅠ,CKMB,MDA and ET levels were increased,the NO,T-SOD levels were decreased in groups C and D(P0.05).Infarct size was significantly reduced,and the myocardial ultrastructural changes were improved significantly in treatment group.Conclusions:Salvianolic acid B has a significant protective effect on myocardial ischemia-reperfusion injury.It can alleviate oxidative stress,reduce calcium overload,improve endothelial function and so on.     

Melatonin attenuates hepatic ischemia-reperfusion injury in rats by inhibiting NF-κB signaling pathway

BackgroundThe sterile inflammatory response is one of the key mechanisms leading to hepatic ischemia-reperfusion injury. Melatonin has been shown to prevent organ injuries, but its roles in the inflammatory response after hepatic ischemia-reperfusion injury have not been fully explored, especially in late ischemia-reperfusion injury. The present study aimed to investigate the roles and possible mechanisms of melatonin in the inflammatory response after hepatic ischemia-reperfusion injury.MethodsSixty Sprague-Dawley rats were randomly divided into a sham group, ischemia-reperfusion injury group (I/R group), and melatonin-treated group (M + I/R group). The rats in the I/R group were subjected to 70% hepatic ischemia for 45 min, followed by 5 or 24 h of reperfusion. The rats in the M + I/R group were injected with melatonin (10 mg/kg, intravenous injection) 15 min prior to ischemia and immediately before reperfusion. Serum and samples of ischemic liver lobes were harvested for future analysis, and the 7-day survival rate was assessed after hepatic ischemia-reperfusion surgery.ResultsIn comparison with the I/R group, the M + I/R group showed markedly decreased expression levels of inflammatory cytokines (IL-6 and TNF-α) and numbers of apoptotic hepatocytes (P < 0.05). Immunoblotting showed that the expression levels of IL-6, p-NF-κBp65/t-NF-κBp65 and p-IκB-α/t-IκB-α in the M + I/R group were significantly lower than those in the I/R group, and immunofluorescence staining showed that the expression level of p-NF-κBp65 in the M + I/R group was lower than that in the I/R group (P < 0.05). The 7-day survival rates were 20% in the I/R group and 50% in the M + I/R group (P < 0.05).ConclusionsMelatonin downregulated the activity of the NF-κB signaling pathway in the early and late stages of hepatic ischemia-reperfusion injury, alleviated the inflammatory response, protected the liver from ischemia-reperfusion injury, and increased the survival rate.     

Effect of intestinal function–recovering decoction on treatment of multiple organ dysfunction syndrome in rats

ObjectiveTo analyze the effect of intestinal function–recovering decoction on multiple organ dysfunction syndrome in rats, and to investigate a novel solution to multiple organ dysfunction syndrome.MethodsMultiple organ dysfunction syndrome was induced in 60 Sprague–Dawley rats by intestinal ischemia–reperfusion combined with cecal ligation and puncture. Then these rats were intragastrically administered physiological saline (group I, n=20), ampicillin (group II, n=20) or intestinal function–recovering decoction (group III, n=20). After treatment, serum malondialdehyde and superoxide dismutase levels were compared among three groups. Simultaneously, bacterial culture of various organ tissues was performed and bacterial and endotoxin translocation were observed.ResultsCompared with group I, serum malondialdehyde, alanine aminotransferase and aspartate aminotransferase levels were significantly decreased (all P<0.05) and serum superoxide dismutase level was significantly increased (P<0.05) in the group III. However, there were no significant differences in these indices between groups II and III (P>0.05). The rate of bacterial translocation in the groups II and III was significantly lower than in the group I (P<0.05), and no significant difference was observed between groups II and III (P>0.05).ConclusionsIntestinal function–recovering decoction can significantly reduce endotoxin and bacterial translocation and stabilize enteral oxidative–antioxidative balance.     

Protective effect of nitric oxide on hepatopulmonary syndrome from ischemia-reperfusion injury

AIM: To evaluate immunological protection of nitric oxide (NO) in hepatopulmonary syndrome and probable mechanisms of ischemia-reperfusion (IR) injury in rat liver transplantation.METHODS: Sixty-six healthy male Wistar rats were randomly divided into three groups (11 donor/recipient pairs). In group II, organ preservation solution was lactated Ringer’s solution with heparin 10  000/μL at 4 °C. In groups I and III, the preservation solution added, respectively, L-arginine or N^G-L-arginine methyl ester (L-NAME) (1 mmol/L) based on group II, and recipients were injected with L-arginine or L-NAME (50 mg/kg) in the anhepatic phase. Grafted livers in each group were stored for 6 h and implanted into recipients. Five rats were used for observation of postoperative survival in each group. The other six rats in each group were used to obtain tissue samples, and executed at 3 h and 24 h after transplantation. The levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF)-α and NO metabolites (NOx) were detected, and expression of NO synthase, TNF-α and intercellular adhesion molecule 1 (ICAM-1) was examined by triphosphopyridine nucleotide diaphorase histochemical and immunohistochemical staining.RESULTS: By supplementing L-arginine to strengthen the NO pathway, a high survival rate was achieved and hepatic function was improved. One-week survival rate of grafted liver recipients in group I was significantly increased (28.8 ± 36.6 d vs 4 ± 1.7 d, P < 0.01) as compared with groups II and III. Serum levels of ALT in group I were 2-7 times less than those in groups II and III (P < 0.01). The cyclic guanosine monophosphate (cGMP) levels in liver tissue and NOx in group I were 3-4 times higher than those of group II after 3 h and 24 h reperfusion, while in group III, they were significantly reduced as compared with those in group II (P < 0.01). The levels of TNF-α in group I were significantly lower than in group II after 3 h and 24 h reperfusion (P < 0.01), while being significantly higher in group III than group II (P < 0.01). Histopathology revealed more severe tissue damage in graft liver and lung tissues, and a more severe inflammatory response of the recipient after using NO synthase inhibitor, while the pathological damage to grafted liver and the recipient’s lung tissues was significantly reduced in group I after 3 h and 24 h reperfusion. A small amount of constitutive NO synthase (cNOS) was expressed in liver endothelial cells after 6 h cold storage, but there was no expression of inducible NO synthase (iNOS). Expression of cNOS was particularly significant in vascular endothelial cells and liver cells at 3 h and 24 h after reperfusion in group II, but expression of iNOS and ICAM-1 was low in group I. There was diffuse strong expression of ICAM-1 and TNF-α in group III at 3 h after reperfusion.CONCLUSION: The NO/cGMP pathway may be critical in successful organ transplantation, especially in treating hepatopulmonary syndrome during cold IR injury in rat orthotopic liver transplantation.     

Protective effect of penehvclidine hvdrochloride on ischemiareperfusion injury in rats

Objective:To investigate the protective effect of penehvclidine hvdrochloride on ischemiareperfusion injury in rats.Method:The model of ischemia-reperniston injury was established in rats through clamping rental pedicles for SO min followed by reperfusion.A total of 60 Wistar rats were randomly divided.into 4 groups including fake surgery group,model group,low PHC dosage group and high dosage penehvclidine hvdrochloride(PHC)group.Seven days before the experiment,rats in fake surgery group and model group were given 10 mL/kg normal saline,while rats in low PHC dosage group and high dosage PHC group were given 200 and SO mg/kg PHC,respectively.The urine volume,diet volume,Cre,PU,BUN,IL-6,IL-8,TNF-α,NO MDA concentration,SOD and GSH-Px were determined.Results:Compared with rats in model group,decreased urine volume,diet volume,Cre,PU,BUN,IL-6,IL-8,TNF-α,NO MDA concentration and increased SOD and CSH-Px activity could be seen in low PHC dosage group and high dosage PHC group(P0.05).Conclusions:Administration of PHC before ischemia-reperfusion injury can help protect ischemia-reperfusion injury.     

The effect of various doses of lazaroid U74389G on lung ischemia reperfusion injury.

BACKGROUND: We investigated the effect of lazaroid U74389G, a potent inhibitor of lipid peroxidation, on ischemia-reperfusion injury at three different doses in the rat orthotopic left lung transplantation model. METHODS: Four groups of reperfused lungs were studied. In group I (control) donor lungs were transplanted after 12 hours of preservation in University of Wisconsin (UW) solution at 4 degrees C. In groups II, III, and IV, lazaroid was used as an additive to UW solution at concentrations of 30 micromol/L, 50 micromol/L, and 100 micromol/L, respectively, and was also administered intravenously to the recipients 30 minutes before reperfusion after 12 hours of storage in the UW solution at 4 degrees C. RESULTS: After 1 hour of reperfusion, gas exchange function (p < 0.01), tissue lipid peroxide levels (p < 0.05) and histologic damage in reperfused lung allografts (p< 0.05) were significantly improved in lazaroid-treated group IV compared with control group I. CONCLUSIONS: These findings suggest that lazaroid U74389G ameliorates ischemia-reperfusion injury in rat lung transplants by inhibiting lipid peroxidation.     

Protection effect of Emodin pretreatment on intestinal I-RI damage of intestinal mucosa in ratsa

Objective:To linvestigate the protective effect and mechanism of emodin pretreatment on intestinal mucosa of rats with intestinal ischemia-reperfusion injury.Methods:A total of 50SD rats were randomly divided into control group,model group,emodin groups of low,medium and high dose,with 10 in each group.Ischemia-reperfusion injury(I-RI)mode was established by using noninvasive clamp on superior mesentericartery(SMA).Control group and model group were pretreated with 0.5%sodium carboxymethyl cellulose solution lavage 2 h before operation,emodin groups of low,medium and high dose were given emodin lavage with 20,40,60 mg/kg pretreatment,femoral venous blood before the lavage pretreatment(TO)and 1 h ischemia(Tl),and inferior vena venous blood after 1 h of reperfusion(T2)were extracted from each group of rats for detection of serun level of intestinal fatty acid binding protein(I-FABP),tumor necrosis factor(TNF-α),endotoxin,interleukin 6(IL-6),and die content of diamine oxidase(DAO);Mter model establishment,the rats were sacrificed,intestine homogenate was prepared by using blind intestinal tissue to detect intestinal tissue myeloperoxidase(MPO],malondialdehyde(MDA)and superoxide dismutase(SOD)levels.And upper small intestine tissue was retrieved,followed by fixation and conventional HE staining to observe intestinal tissue morphology under light microscopy.Results:In emodin groups of low,medium and high dose at T1 and T2,I-FABP,TNF-α,endotoxin.IL,-6 and DAO level were significandy lower than that of model group(P0.05);in emodin group of low,medium and high dose,MPO and MDA content in intestinal tissue homogenate was significantly lower than that in model group(P0.05),SOD level was significantly higher than that of model group(P0.05).Intestinal damage of emodin low,medium and high dose groups were significandy lighter than model group.Conclusions:Emodin pretreatment has certain protective effect on intestinal mucosa in ischemia reperfusion injury.     

Effects of salidroside pretreatment on expression of tumor necrosis factor-alpha and permeability of blood brain barrier in rat model of focal cerebralischemia-reperfusion injury

ObjectiveTo observe changes in expression of tumor necrosis factor (TNF)-alpha and permeability of blood brain barrier after salidroside pretreatment in rats with injury induced by focal cerebralischemia-reperfusion.MethodsForty-five male SD rats were randomly divided into three groups (n=15): control group, ischemia-reperfusion (IR) model group, and salidroside pretreatment group. Before the IR model establishment, the rats in the salidroside pretreatment group were intraperitoneally administered with salidroside at a dose of 24 mg/(kg·d) for 7 d. After 30 min post the last administration, the IR model was induced by occlusion of middle cerebral artery with a filament. After 24 h post the operation, the water content and Evens blue content in the ischemia cerebral hemisphere were determined, and the level of TNF-alpha mRNA was detected by the semi-quantitative RT-PCR.ResultsCompared with the IR model group, the salidroside pretreatment group had significantly lower (P<0.05) water content and Evens blue content in the ischemia cerebral hemisphere and also had significantly lower (P<0.05) level of TNF-alpha in the ischemic cerebral cortex tissue.ConclusionsThe salidroside pretreatment alleviated the focal cerebralischemia-reperfusion injury in the rat model, possibly by decreasing the permeability of blood brain barrier, attenuating brain edema and reducing TNF-alpha expression.     

肾缺血再灌注损伤大鼠肺内CAT的表达变化

目的 观察肾缺血再灌注损伤大鼠肺内过氧化氢酶(catalase,CAT)的表达变化,探讨CAT在抗氧化应激反应中的作用.方法 大鼠切除右肾,无损伤动脉夹夹闭左肾动脉,建立肾缺血再灌注损伤模型.再灌注24 h后取材(血、肾、肺).酶偶联速率法和苦味酸法分别检测血尿素氮(blood urea nitrogen,BUN)、血清肌酐(serum creatinine,SCr)浓度;HE染色法观察大鼠肾形态;硫代巴比妥酸比色法检测肺内丙二醛(malondialdehyde,MDA)的含量;采用RT-PCR和Western blot方法分别测定大鼠肺组织内抗氧化酶CAT的mRNA与蛋白表达水平.结果 HE结果显示肾缺血再灌注损伤组大鼠的肾组织受损明显.与对照组相比,肾缺血再灌注损伤组血清中的BUN和SCr、肺组织中的MDA含量均明显升高(P<0.05或P<0.01),CAT的mRNA表达水平与蛋白表达水平均明显升高(P值均<0.01).结论 肾缺血再灌注损伤后,肺内发生了过氧化损伤.CAT在肾缺血再灌注损伤大鼠肺内发挥了抗氧化应激的作用.     

Influence of Ketotifen, Cromolyn Sodium, and Compound 48/80 on the survival rates after intestinal ischemia reperfusion injury in rats

Background

Mast cells were associated with intestinal ischemia-reperfusion injury, the study was to observe the influence of Ketotifen, Cromolyn Sdium(CS), and Compound 48/80(CP) on the survival rates on the third day after intestinal ischemia-reperfusion injury in rats.

Methods

120 healthy Sprague-Dawley rats were randomly divided into 5 groups, Sham-operated group (group S), model group (group M), group K, group C and group CP. Intestinal damage was triggered by clamping the superior mesenteric artery for 75 minutes, group K, C, and CP were treated with kotifen 1 mg·kg^-1, CS 50 mg·kg^-1, and CP 0.75 mg·kg^-1 i.v. at 5 min before reperfusion and once daily for three days following reperfusion respectively. Survival rate in each group was recorded during the three days after reperfusion. All the surviving rats were killed for determining the concentration of serum glutamic-oxaloacetic transaminase(AST), glutamic pyruvic transaminase(ALT), the ratio of AST compare ALT(S/L), total protein(TP), albumin(ALB), globulin(GLB), the ratio of ALB compare GLB(A/G), phosphocreatine kinase(CK), lactate dehydrogenase(LDH), urea nitrogen(BUN) and creatinine(CRE) at the 3^rd day after reperfusion. And ultrastructure of IMMC, Chiu's score, lung histology, IMMC counts, the levels of TNF-α, IL-1β, IL-6 and IL-10 of the small intestine were detected at the same time.

Results

Intestinal ischemia-reperfusion injury reduced the survival rate. The concentrations of TP, ALB and level of IL-10 in intestine in group M decreased significantly while the concentrations of S/L, LDH and the levels of IL-6 and TNF-α in intestine increased significantly compared with group S (P < 0.05). Treatment with Ketotifen and CS increased the survival rate compared with group M (P < 0.05), attenuated the down-regulation or up-regulation of the above index (P < 0.05). Treatment with CP decreased the survival rate on the 3^rd day after reperfusion compared with group M(P < 0.05). Group K and C had better morphology in IMMC in the small intestine and in the lungs than in group M and CP, although the Chiu's score and IMMC counts remained the same in the five groups(P > 0.05).

Conclusion

Mast cell inhibition after ischemia prior to reperfusion and following reperfusion may decrease the multi-organ injury induced by intestine ischemia reperfusion, and increase the survival rates.     

白细胞介素8在大鼠脑缺血再灌注损伤中的变化

目的探讨白细胞介素8在大鼠脑缺血再灌注损伤中的变化.方法参照Zea Longa线栓法制作急性大鼠大脑中动脉缺血再灌注模型,将大鼠随机分为假手术组和脑缺血1h再灌注3、6、12、24及48h组,采用双抗体夹心间接酶联免疫吸附法检测大鼠血清和脑组织中白细胞介素8的浓度.结果血清中白细胞介素8含量于再灌注3h达最高(P＜0.01),随后缓慢下降,再灌注24h降至对照水平;脑组织中白细胞介素8含量于再灌注6h达高峰(P＜0.01),再灌注12h后下降,但再灌注6h与12h之间无显著性差异.结论白细胞介素8参与了脑缺血再灌注损伤的病理生理过程.     

Metalloproteinase expression after desflurane preconditioning in hepatectomies: A randomized clinical trial

BACKGROUNDHepatectomy with inflow occlusion results in ischemia-reperfusion injury; however, pharmacological preconditioning can prevent such injury and optimize the postoperative recovery of hepatectomized patients. The normal inflammatory response after a hepatectomy involves increased expression of metalloproteinases, which may signal pathologic hepatic tissue reformation. AIMTo investigate the effect of desflurane preconditioning on these inflammatory indices in patients with inflow occlusion undergoing hepatectomy.METHODSThis is a single-center, prospective, randomized controlled trial conducted at the 4^th Department of Surgery of the Medical School of Aristotle University of Thessaloniki, between August 2016 and December 2017. Forty-six patients were randomized to either the desflurane treatment group for pharmacological preconditioning (by replacement of propofol with desflurane, administered 30 min before induction of ischemia) or the control group for standard intravenous propofol. The primary endpoint of expression levels of matrix metalloproteinases and their inhibitors was determined preoperatively and at 30 min posthepatic reperfusion. The secondary endpoints of neutrophil infiltration, coagulation profile, activity of antithrombin III (AT III), protein C (PC), protein S and biochemical markers of liver function were determined for 5 d postoperatively and compared between the groups.RESULTSThe desflurane treatment group showed significantly increased levels of tissue inhibitor of metalloproteinases 1 and 2, significantly decreased levels of matrix metalloproteinases 2 and 9, decreased neutrophil infiltration, and less profound changes in the coagulation profile.  During the 5-d postoperative period, all patients showed significantly decreased activity of AT III, PC and protein S (vs baseline values, P < 0.05). The activity of AT III and PC differed significantly between the two groups from postoperative day 1 to postoperative day 5 (P < 0.05), showing a moderate drop in activity of AT III and PC in the desflurane treatment group and a dramatic drop in the control group. Compared to the control group, the desflurane treatment group also had significantly lower international normalized ratio values on all postoperative days (P < 0.005) and lower serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase values on postoperative days 2 and 3 (P < 0.05).   Total length of stay was significantly less in the desflurane group (P = 0.009).CONCLUSIONDesflurane preconditioning can lessen the inflammatory response related to ischemia-reperfusion injury and may shorten length of hospitalization.     

R56865, a Na- and Ca-Overload Inhibitor, Reduces Myocardial Ischemia-Reperfusion Injury in Blood-Perfused Rabbit Hearts

The cardioprotective effects of R56865 were studied in isolated rabbit hearts, blood-perfused with a support rabbit system. The effect on ischemic injury was evaluated by comparing myocardial contracture and contents of ATP catabolites and of lactate during 60 min of normothermic ischemia in untreated hearts (group I) and in hearts treated with 0.63 mg/kg of R56865 starting 20 min before ischemia (group II; n = 5 in each group). R56865 delayed the onset, and decreased the extent of ischemic contracture, but had no effect on the myocardial content of ATP, of its catabolites or of lactate. The effect on reperfusion injury was studied by monitoring left ventricular function during 80-min reperfusion after the 60-min ischemia in three groups (n = 6 in each): an untreated group (group I) and two groups treated with R56865 given either before (group II) or after ischemia (group III). Ultrastructural changes and cellular calcium distribution after reperfusion were also studied. R56865 improved the recovery of function and prevented contracture during reperfusion. Left ventricular end-diastolic pressure was 13.2 ± 2.8 mmHg in group II and 31.3 ± 8.1 mmHg in group III vs 45.0 ± 2.6 mmHg in group I (P < 0.0001 for II vs I; P > 0.05 for III vs I). Left ventricular developed pressure, maximum dP/dt and minimum dP/dt recovered to 71.0 ± 5.4%, 98.9 ± 6.1%, 85.3 ± 4.8% of baseline values, respectively, in group II, to 64.5 ± 3.0% (P > 0.05), 76.8 ± 3.0%, 70.2 ± 4.0% in group III, vs 52.0 ± 6.5%, 58.9 ± 6.9% and 53.6 ± 5.8% in untreated hearts (P < 0.05 for II or III vs I). Coronary flow was 24.5 ± 2.2 ml/min and 19.8 ± 1.8 ml/min in groups II and III vs 14.8 ± 0.7 ml/min (P < 0.05) in the untreated group. On histology the myocardium in hearts treated either before after ischemia was well protected and calcium distribution was almost normal after reperfusion, while in untreated hearts, most of the myocardium displayed irreversible damage accompanied by massive intracellular calcium accumulation. We conclude that R56865 could attenuate Ca²⁺-overload, thereby reducing myocardial ischemia-reperfusion injury after an extended period of ischemia.     

Effect of atorvastatin on serum oxidative stress and N-terminal brain natriuretic peptide expression in rats

Objective:To investigate the effect of atorvastatin on serum oxidative stress and N-terminal brain natriuretic peptide expression in rats.Methods:A total of 40 healthy male SD rats were randomly divided into the sham group(Croup A,n=10,saline 5 mL/d),ischemia-reperfusion group(Group B,n=10,saline S mL/d),atorvastatin group(Group C,n=10.atorvastatin 20 mg/kg·d),atorvastatin + N-amino-arginine group(Group D,n=10,atorvastatin 20 mg/kg·d + N-amino arginine 15 mg/kg).Myocardial ischemia-reperfusion rat model was eslablished after 3 days of gavage.N-amino arginine 15 mg/kg was given by tail vein injection 15 min before ischemia.After reperfusion,enzymology indicators such us creatine kinase(CK) and lactate dehydrogenase and the oxidative stress parameters such as nitric oxide(NO),malondialdehyde(MDA) and total superoxide dismutase(TSOD),and n-terminal pro-brain natriuretic peptide(NT-proBNP)expression was detected by immunohistochemistry.Results:LDH and CK levels of group A were significantly lower than the outer three groups,and group B was the highest.There was significant difference between group B and group C(P0.05),and no significant difference between group B and group D(P0.05).MDA levels in group B were significantly higher than the other three groups.The lowest was group A,followed by group C,the difference among groups was significantly(P0.05).TSOD and NO levels in group B was the lowest,the level in group A was the highest,followed by group C,the difference among groups was significant(P0.05).NT-proBNP level in group B was significantly higher than the other three groups,the lowest was group A,followed by group C,the difference among groups was significant(P0.05).Conclusions:Atorvastatin has a protective effect on the myocardial injury in the myocardial ischemia and reperfusion rats.It can increase NO synthesis and decrease MDA content,increase serum TSOD activity and the oxidative stress effect,meanwhile protect myocardial cells and reduce myocardial injury.     

Glutamine prevents oxidative stress in a model of mesenteric ischemia and reperfusion

AIM: To evaluate preventative effects of glutamine in an animal model of gut ischemia/reperfusion (I/R).METHODS: Male Wistar rats were housed in a controlled environment and allowed access to food and water ad libitum. Twenty male Wistar rats were divided into four experimental groups: (1) control group (control) - rats underwent exploratory laparotomy; (2) control + glutamine group (control-GLU) - rats were subjected to laparotomy and treated intraperitoneally with glutamine 24 and 48 h prior to surgery; (3) I/R group - rats were subjected to occlusion of the superior mesenteric artery for 30 min followed by 15 min of reperfusion; and (4) ischemia/reperfusion + glutamine group (G + I/R) - rats were treated intraperitoneally with glutamine 24 and 48 h before I/R. Local and systemic injuries were determined by evaluating intestinal and lung segments for oxidative stress using lipid peroxidation and the activity of superoxide dismutase (SOD), interleukin-6 (IL-6) and nuclear factor kappa beta (NF-κB) after mesenteric I/R.RESULTS: Lipid peroxidation of the membrane was increased in the animals subjected to I/R (P < 0.05). However, the group that received glutamine 24 and 48 h before the I/R procedure showed levels of lipid peroxidation similar to the control groups (P < 0.05). The activity of the antioxidant enzyme SOD was decreased in the gut of animals subjected to I/R when compared with the control group of animals not subjected to I/R (P < 0.05). However, the group that received glutamine 24 and 48 h before I/R showed similar SOD activity to both control groups not subjected to I/R (P < 0.05). The mean area of NF-κB staining for each of the control groups was similar. The I/R group showed the largest area of staining for NF-κB. The G + I/R group had the second highest amount of staining, but the mean value was much lower than that of the I/R group (P < 0.05). For IL-6, control and control-GLU groups showed similar areas of staining. The I/R group contained the largest area of IL-6 staining, followed by the G + I/R animals; however, this area was significantly lower than that of the group that underwent I/R without glutamine (P < 0.05).CONCLUSION: These results demonstrate that pretreatment with glutamine prevents mucosal injury and improves gut and lung recovery after I/R injury in rats.     

Bradykinin B2 Receptor Antagonist FR173657 Ameliorates Small Bowel Ischemia–Reperfusion Injury in Dogs

Bradykinin mediates acute inflammation by increasing microvascular permeability, vasodilation, leukocyte migration and accumulation, and the production of arachidonic acid via phospholipase A₂ activation. Arachidonic acid metabolites, or eicosanoids, are potent modulators of biological functions, particularly inflammation. Bradykinin exerts its inflammatory effects via the bradykinin B₂ receptor. The aim of this study was to evaluate the effect of a bradykinin B₂ receptor antagonist, FR173657 (FR), on intestinal ischemia-reperfusion (I/R) injury. Twenty-eight mongrel dogs were divided into four groups (n = 7 per group). Group I underwent I/R alone, Group II underwent I/R and received FR treatment, Group III was sham operated, and Group IV was sham operated and received FR treatment. The FR treatment consisted of FR continuously from 30 min prior to ischemia to 2 hr after reperfusion. In the I/R procedure, the superior mesenteric artery (SMA) and vein were clamped for 2 hr and then released to permit reperfusion for 12 hr. The intramucosal pH (pH_i), SMA blood flow, and mucosal tissue blood flow were measured during the reperfusion period. The serum thromboxane B₂ and 6-keto-prostaglandin F₁ levels were determined, and tissue samples were examined histologically. Results showed that tissue blood flow, pH_i, and SMA blood flow after reperfusion were maintained in Group II in comparison with Group I. Histopathological examination showed less severe mucosal damage after reperfusion in Group II than in Group I. The serum thromboxane B₂ and 6-keto-prostagland in F₁ levels were significantly lower in Group II than in Group I (P < 0.05). We conclude that FR treatment appears to have clear protective effects on small bowel I/R injury by inhibiting the release of eicosanoids.     

Expression and significance of MMP3 in synovium of knee joint at different stage in osteoarthritis patients

Objective:To investigate the expression and significance of MMP-3 in synovium of knee joint at different stage in osteoarthritis(OA)patients.Methods:Knee synovial tissue were collected in90 OA patients(the OA group).Patients in the OA group was divided into 3 subgroups:gradeⅠsubgroup(n=30),gradeⅡsubgroup(n=30),gradeⅢsubgroup(n=30).Thirty patients served as control group,lmmunohistochemical assay was used to detect the expression of MMP-3 protein in the knee synovial tissue.Results:MMP-3 protein was detected in all knee synovial tissue.The expression of MMP-3 protein in the OA group was significantly higher that in the normal synovium(P0.05),and the MMP-3 protein was mainly located in the cytoplasm.There was significant difference in the expression of MMP-3 protein between the gradeⅢsubgroup and the gradeⅠ,gradeⅡsubgroups(all P0.05).The expression of MMP-3 protein was positively related to the severity of OA(r=0.912,P0.05).Conclusions:The expression of MMP-3 protein are closely related to pathogenic mechanism of OA.It may be an important indicator of early diagnosis and the activity of the disease of osteoarthritis.