Protective effects of carvedilol on ischemia–reperfusion injury in rat epigastric island skin flaps

Carvedilol, a selective alpha-1 and nonselective beta-adrenoceptor antagonist and potent antioxidant, has been shown to provide a significant decrease in neutrophil-mediated tissue injury. Epigastric skin flaps were elevated in rats, rendered ischemic for 10 h, and subsequently reperfused for 12 h. Forty rats were divided into four equal experimental groups: 1—nonischemic group, 2—ischemic saline control group, 3—ischemic control group without any vehicle treatment, and 4—drug-administered ischemic group. The effects of carvedilol on flap necrosis, neutrophil infiltration, and levels of malondialdehyde and nitric oxide in the flap tissue and serum were examined. The authors found that neutrophil numbers were significantly higher in the saline and nontreated groups. Additionally, serum and tissue levels of malondialdehyde were lower in the carvedilol-treated group, and serum nitric oxide was highest in the carvedilol-treated group. Carvedilol-treated animals had significantly lower areas of necrosis compared with controls. We conclude that administration of carvedilol before ischemia and reperfusion can significantly reduce the extent of flap necrosis and flap neutrophil counts because of ischemia–reperfusion injury. This study was presented at the 28th National Congress of Turkish Plastic, Reconstructive and Aesthetic in Ankara, Turkey, September 20–23, 2006.     

Protective effect of a novel NO-donor on ischemia/reperfusion injury in a rat epigastric flap model

An altered metabolism of endothelial cell-derived nitric oxide has been implicated in the microvascular dysfunction associated with ischemia/reperfusion. The objective of this study was to examine whether S-nitroso human serum albumin, a novel nitric oxide-donor, improves flap viability and whether it influences edema formation after prolonged ischemia when administered prior to and in the initial phase of reperfusion. Denervated epigastric island skin flaps were elevated in 30 male Sprague Dawley rats, rendered ischemic for 8 hours, subsequently reperfused and further observed for either 3 hours (acute) or 7 days (chronic). In the sham rats (n = 6), skin flaps were elevated only. Starting 1 hour prior to reperfusion, S-nitroso human serum albumin (n = 12) or human serum albumin (n = 12) as placebo was infused systemically for 2 hours. In the chronic model, flap necrosis as well as viable flap size was evaluated after 7 days of reperfusion in six rats per group, comparing to sham rats. In the acute model, edema formation was evaluated after 3 hours of reperfusion in six rats per group. Administration of S-nitroso human serum albumin significantly decreased flap necrosis from 18.1 +/- 15.6% in the human serum albumin group to 2.1 +/- 1.5% in the S-nitroso human serum albumin group, which was similar to the sham group (2.5 +/- 4.2%). Viable flap size (sham 13.4 +/- 1.6 cm2) was also significantly improved in the S-nitroso human serum albumin group (10.1 +/- 1 cm2) versus the human serum albumin group (7.0 +/- 2.2 cm2). There was no significant difference between the groups regarding postischemic edema formation. These results show that administration of S-nitroso human serum albumin prior to and in the initial phase of reperfusion significantly improves flap viability after 7 days but does not influence early observable edema formation. These findings support the role of nitric oxide as an important mediator in the protection against skin flap ischemia/reperfusion injury.     

Tadalafil significantly reduces ischemia reperfusion injury in skin island flaps

Introduction:

Numerous pharmacological agents have been used to enhance the viability of flaps. Ischemia reperfusion (I/R) injury is an unwanted, sometimes devastating complication in reconstructive microsurgery. Tadalafil, a specific inhibitor of phosphodiesterase type 5 is mainly used for erectile dysfunction, and acts on vascular smooth muscles, platelets and leukocytes. Herein, the protective and therapeutical effect of tadalafil in I/R injury in rat skin flap model is evaluated.

Materials and Methods:

Sixty epigastric island flaps were used to create I/R model in 60 Wistar rats (non-ischemic group, ischemic group, medication group). Biochemical markers including total nitrite, malondialdehyde (MDA) and myeloperoxidase (MPO) were analysed. Necrosis rates were calculated and histopathologic evaluation was carried out.

Results:

MDA, MPO and total nitrite values were found elevated in the ischemic group, however there was an evident drop in the medication group. Histological results revealed that early inflammatory findings (oedema, neutrophil infiltration, necrosis rate) were observed lower with tadalafil administration. Moreover, statistical significance (P < 0.05) was recorded.

Conclusions:

We conclude that tadalafil has beneficial effects on epigastric island flaps against I/R injury.KEY WORDS: Free radicals, ischemia, island flap, reperfusion injury, tadalafil     

Protective effects of some antineoplastic agents on ischemia-reperfusion injury in epigastric island skin flaps

Neutrophil depletion has a beneficial effect on ischemic myocardium and skeletal muscle upon reperfusion. Antineoplastic agents reduce blood neutrophils effectively, and lead to neutrophil depletion. The purpose of this study was to investigate the effects of four antineoplastic agents in low doses (cyclophosphamide, cisplatinum, mitomycin-C, and 5-fluorouracil) on ischemia-reperfusion injury, using an epigastric island skin-flap model in rats. Fifty male Sprague-Dawley rats, weighing 250-300 g, were randomly divided into five groups, each consisting of 10 rats: control, cyclophosphamide, cisplatinum, mitomycin-C, and 5-fluorouracil groups. Epigastric island skin flaps (measuring 3.5 x 4 cm) were raised and subjected to 10 h of in situ ischemia, followed by 7-day reperfusion and evaluation. Treatment with antineoplastic agents (cyclophosphamide, cisplatinum, mitomycin-C, and 5-fluorouracil) was used to introduce neutropenia. Complete blood counts, cutaneous bleeding time, and skin-flap survival were evaluated. Additionally, levels of malonyldialdehyde (MDA), nitric oxide (NO), glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were measured from extracted skin tissue. Numbers of leukocytes and platelets were decreased in all experimental groups. However, neutropenia and thrombocytopenia were not seen. Cutaneous bleeding activity was prolonged in all experimental groups, but not above the normal value. MDA and NO levels were found to be lower in all four antineoplastic agent groups than in the control group, while GSH, GSH-Px, and SOD enzyme activities were significantly higher (P < 0.05). However, MDA and NO levels were significantly decreased in the cyclophosphamide and 5-fluorouracil groups, as compared to the cisplatinum and mitomycin-C groups (P < 0.01). Also, GSH, GSH-Px, and SOD enzyme activities were significantly increased in the cyclophosphamide and 5-fluorouracil groups, compared to the other two antineoplastic agent groups (P < 0.01). We conclude that antineoplastic agents have beneficial effects on ischemia-reperfusion injuries when their doses are carefully adjusted, by decreasing the number of leukocytes and platelets, and altering the activity of free oxygen radicals.     

Effect of specific neutrophil elastase inhibitor on ischemia/reperfusion injury in rat liver transplantation.

Activated neutrophils have been implicated as playing an important role in ischemia/reperfusion injury of the liver by releasing toxic mediators such as oxygen free radicals and elastases. In the present study, we evaluated the effect of a novel, specific neutrophil elastase inhibitor (ONO-5046) on cold-ischemia/reperfusion injury of the liver allograft in rodents. Livers from male Lewis rats were procured and stored cold (4 degrees C) in lactated Ringer's solution and transplanted orthotopically. Recipients were divided into three groups: Vehicle group, 5-h preservation and vehicle (n = 8); ONO-5046 group, 5-h preservation and administration of ONO-5046 (n = 8); and Control group, minimum preservation only (n = 8). Bile output after reperfusion was significantly larger in the ONO-5046 group compared to the Vehicle group (P < 0.05 or less). Sinusoidal endothelial cell function represented by the serum hyaluronic acid concentration at 120 min after reperfusion of the ONO-5046 group was significantly lower than that in the Vehicle group (17.0 +/- 7.9 vs 36.2 +/- 14.9 ng/ml, P < 0.05), whereas serum transaminase levels 120 min after reperfusion were comparable between the two groups. Liver tissue energy charge 120 min after reperfusion was significantly better in the ONO-5046 group compared to the Vehicle group (P < 0.05). Furthermore, the number of neutrophils infiltrating the allograft after reperfusion was significantly depressed in the ONO-5046 group compared to the Vehicle group (P < 0. 02). These data suggest that the neutrophil elastase might cause liver damage early after reperfusion in cold-stored liver, which can be ameliorated by the administration of a specific neutrophil elastase inhibitor, ONO-5046.     

Protective effect of a nuclear factor-kappaB inhibitor on ischemia-reperfusion injury in a rat epigastric flap model

We examined whether nuclear factor-kappa B (NF-kappaB) activation was involved in the ischemia-reperfusion (I/R) injury in a rat skin flap model and whether administration of pyrrolidine dithiocarbamate (PDTC), a NF-kappaB inhibitor, could improve flap viability. Eighty-four Sprague-Dawley rats were divided into control group (n = 28), I/R group (n = 28), and PDTC-treated group (n = 28). An abdominal skin flap (4 x 5 cm) was elevated and subjected to 10 hours of ischemia in both the I/R group and the PDTC-treated group. A bolus of PDTC (300 mg/kg) was infused 5 minutes before reperfusion, followed by a second dose during the first 30 minutes of reperfusion in the PDTC-treated group. Flap tissues were assessed by electrophoretic mobility shift assay at 1, 2, 3, and 6 hours of reperfusion, and myeloperoxidase activity and neutrophil infiltration were assessed at 12 hours of reperfusion. The viability of flaps was assessed 7 days postoperatively. NF-kappaB was activated after reperfusion in the I/R group and displayed peak activity at 1 and 3 hours of reperfusion. In the PDTC-treated group, NF-kappaB activity was significantly reduced at 1, 2, and 6 hours of reperfusion. Myeloperoxidase activity was significantly decreased, and little neutrophil infiltration could be observed. In the PDTC-treated group, the survival of flaps was 86.88 +/- 13.63%, which was significantly greater than the I/R group, in which only 19.20 +/- 7.52% of the flap survived. NF-kappaB is activated during reperfusion in a rat skin flap I/R model. Administration of PDTC can significantly improve flap survival by regulating the early activation of NF-kappaB and suppressing neutrophil infiltration within the flap.     

依达拉奉对大鼠肝I/R损伤的保护作用

目的探讨依达拉奉对大鼠肝缺血再灌注(I/R)损伤中的保护作用。方法将60只大鼠随机分为实验组和对照组,建立常温下部分肝脏I/R动物模型。在肝脏I/R开始时和1 h后对实验组大鼠给予依达拉奉注射液,对照组给予同等容量的生理盐水。再灌注0,2,4 h测定肝脏脂质过氧化反应物(LPO)浓度和肝脏酶学指标及TNF-α和E-selectin的mRNA,并行两组肝脏的病理学检查。结果再灌注2,4 h实验组大鼠肝脏LPO反应程度和肝脏酶指标检测值明显低于对照组(P0.05)。再灌注2 h肝TNF-αmRNA和E-selectinmRNA表达明显低于对照组(P0.05)。再灌注2 h实验组大鼠肝脏切片的E-selectin免疫反应性明显低于对照组。结论依达拉奉能抑制氧化应激反应,从而降低肝I/R损伤;并显著减少炎性细胞和黏附分子的产生,抑制炎性反应的发生。     

Protective effect of an inhibitor of interleukin-8 (meraxin) from ischemia and reperfusion injury in a rat model of kidney transplantation

INTRODUCTION: Since the ischemia and reperfusion injury is one of the main causes of delayed graft function after transplantation, research efforts have focused on studying the molecules involved in this inflammatory process. The chemokine interleukin-8 (IL-8) seems to be the main one responsible through a chemoattractive action toward neutropils. Therefore, one of the strategies adopted to prevent this process is blocking the binding between IL-8 and its receptors. The aim of our study was to test the effect of meraxin, a new derivative from repertaxin, to protect the renal graft from ischemia and reperfusion injury. MATERIALS AND METHODS: Eighty male syngenic rats were divided into four groups. The control group underwent only kidney transplantation, while the other groups were treated with meraxin at various dosages 2 hours before graft reperfusion. Blood and histological samples were taken at sacrifice 24 hours after transplantation. RESULTS: Creatinine was significantly lower in the group treated with the high dosage of meraxin. Histological observation of the grafted tissue showed instead only a mild and not significant neutrophilic infiltration, equal in each group. CONCLUSIONS: Graft function was improved by the administration of meraxin at high dosage, but this effect did not seem to be connected to a reduction in inflammatory infiltration in the parechymal tissue. Maybe the cause is in the mechanisms of clotting activation, due to alteration of adhesion molecules and endothelial cells.     

Protective effect of tadalafil on ischemia/reperfusion injury of rat ovary

Background/Purpose

The aim of the study was to evaluate the effects of tadalafil (TDF) on ischemia/reperfusion (I/R) injury in rat ovaries.

Methods

Thirty-five female Sprague-Dawley rats were randomly divided into 5 groups (n = 7): sham (S), I/R1, I/R2, TDF1, and TDF2. In the I/R1 and TDF1 groups, 3-hour ischemia was followed by 12-hour reperfusion; and in the I/R2 and TDF2 groups, 3-hour ischemia was followed by 24-hour reperfusion. In the TDF groups, 30 minutes before reperfusion, a single dose of 5 mg/kg TDF was administered intraperitoneally. The ovarian tissue levels of malondialdehyde and nitric oxide (NO), and the activities of superoxide dismutase and catalase were measured biochemically. Tissue damage to ovarian tissue was scored by histopathologic examination.

Results

The tissue malondialdehyde levels were significantly higher and the catalase and superoxide dismutase activities were significantly lower in the I/R groups compared with the S and TDF groups (P < .05). The NO levels were significantly higher in the TDF1 group than the S and I/R1 groups (P < .05). Although the NO levels were increased in the TDF2 group compared with the I/R2 group, the difference was not significant. Ovarian tissue damage scores of the I/R groups were significantly higher than those of the S group (P < .05). Treatment with TDF significantly decreased the ovarian tissue damage scores in the TDF groups compared with the I/R groups (P < .05).

Conclusions

Tadalafil is effective in preventing tissue damage induced by I/R in rat ovaries.     

Intermedin预处理对大鼠肾缺血离体再灌注损伤的保护作用

目的:探讨IMD预处理对大鼠肾缺血再灌注(ischemia/reperfusion,I/R) 伤的保护作用.方法:用动脉夹夹闭大鼠左侧肾蒂1 h再灌注1 h的手术方法制成急性肾缺血再灌注损伤动物模型,将动物分为对照组、肾I/R组、IMD高、低剂量预防组、ADM预防组,检测离体肾脏流出液量及其中乳酸脱氢酶(LDH)含量、肾脏组织过氧化氢酶(CAT)、总超氧化物歧化酶(T-SOD)活性和丙二醛(MDA)含量,肾组织光镜下形态学观察.结果:与单纯肾I/R组相比,IMD高、低剂量组和ADM组均显著增加了离体肾脏流出液量(P<0.01),均显著降低了乳酸脱氢酶活性(P<0.01),均显著增加了离体肾脏的T-SOD和CAT活性(P<0.001);且IMD低剂量组的作用更加显著(P<0.05),均明显抑制了MDA的生成(P%0.001),形态学显示肾I/R组肾小球结构异常,细胞坏死、混浊肿胀或凋亡,基底膜剥脱,IMD高、低剂量组和ADM组肾小球结构基本正常,仅有中、重度空泡形成(P<0.01).结论:IMD、ADM预处理对肾I/R损伤有保护作用,其机制可能与清除自由基、减轻脂质过氧化有关.     

Protective effect of N-acetylcysteine on renal ischemia/reperfusion injury in the rat

BACKGROUND: Oxygen free radicals are important components involved in the pathophysiological tissue alterations observed during ischemia/reperfusion (I/R). METHODS: The protective effect of N-acetylcysteine (NAC) against the damage inflicted by reactive oxygen species during renal I/R was investigated in Wistar Albino rats using biochemical parameters. Animals were unilaterally nephrectomized, and subjected to 45 min of renal pedicle occlusion followed by lh of reperfusion. N-acetylcysteine (150 mg/kg, i.p.) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion period, rats were killed by decapitation. For biochemical analysis, the lipid peroxidation product malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and protein oxidation (PO) were tested. Serum creatinine and BUN concentrations were measured for the evaluation of renal function. RESULTS: I/R induced nephrotoxicity, as evidenced by increases in BUN and creatinine, was reversed by NAC. The decrease in GSH and increases in MDA, MPO and PO induced by I/R indicated that renal injury involves free radical formation. CONCLUSIONS: Since NAC reversed these oxidant responses, and protected rat renal proximal tubules from in vitro simulated reperfusion injury, it seems that NAC protects kidney tissue against oxidative damage.     

Protective effect of glycine in mesenteric ischemia and reperfusion injury in a rat model

PURPOSE: Glycine has a protective effect in renal and skeletal muscle ischemia. The purpose of this study was to evaluate the effect of glycine in mesenteric ischemia and reperfusion injury in a rat model. METHODS: Twenty-four anesthetized male Sprague-Dawley rats were subjected to 1 hour of mesenteric ischemia followed by 2 hours of reperfusion. Control animals received normal saline solution intravenously at 0.01 mL/g of body weight/h during ischemia and reperfusion. Treated animals received glycine at 0.5, 0.75, or 1.0 mg/g of body weight, dissolved in saline solution and infused at 0.01 mL/g/h for 2 hours. Animals were killed at the end of the experiment, and proximal, middle, and distal segments of the small bowel were isolated. Sections of the segments stained with hematoxylin-eosin were subjected to histologic examination (as per modified Chiu grading system) and morphometric analysis consisting of measurement of bowel wall, muscularis and mucosal thickness, epithelial coverage, and villar circumference. Isometric tension responses to electrical stimulation (10, 30, 50, 100 Hz), high doses of potassium (120 mmol/L), and carbachol (0.1, 0.5, 1.0, 5.0 micromol/L) were recorded in a multimuscle chamber. Statistical analysis was performed with unpaired t test and one-way analysis of variance. RESULTS: The middle and distal segments of the small bowel in glycine-treated animals showed better histologic grade compared with saline solution-treated control rats (P <.05). At morphometric analysis, total thickness, mucosal thickness, and villar circumference ratio were well preserved in the middle and distal segments of the small bowel in the glycine-treated group (P <.05). No significant differences were observed in the proximal bowel segments between glycine-treated and control animals, because the proximal segment was not subjected to much ischemia. No differences were noted in percentage of epithelial coverage. Isometric tension responses evoked by electrical stimulation were greater (P <.05) in the middle and distal segments treated with glycine as compared with control segments. Carbachol-evoked contractions were stronger (P <.05) in the small bowel segments of animals treated with glycine. The responses evoked by 120 mmol/L of potassium were stronger in the distal segments of the small bowel in the glycine-treated group (P <.05). This cytoprotective effect of glycine was not dose-dependent. CONCLUSIONS: Glycine improved mucosal viability in the ischemia and reperfusion injury rat model. Mucosal thickness and villous circumference ratio were reliable objective parameters for evaluation of intestinal ischemia injury. Glycine improved the contractile responses of the bowel segments also, probably by altering the physiologic mechanisms underlying force generation. Further studies are required to elucidate the mechanism of the cytoprotective action of glycine.     

NFκB抑制剂对大鼠肝脏移植再灌注损伤的保护作用

目的　探讨大鼠肝脏移植后核因子κB(NFκB)活化对炎性介质表达和中性粒细胞浸润集聚的影响。方法　供受体鼠分别于术前 15min腹腔注射NFκB抑制剂脯氨酸二硫代氨基甲酸酯 (ProDTC 15mg/kg)。 结果　与对照组相比 ,应用ProDTC者移植后NFκBp6 5含量、肿瘤坏死因子 α(TNF α)、巨噬细胞炎性蛋白 2 (MIP 2 )、细胞间粘附分子 1(ICAM 1)mRNA表达和蛋白表达明显下降 ;髓过氧化物酶 (MPO)活性明显减低 (P均 <0 0 1)。ProDTC也显著降低天门冬氨酸转氨酶(AST)、丙氨酸转氨酶 (ALT)、乳酸脱氢酶 (LDH)水平 (P <0 0 1)。结论　ProDTC抑制移植后NFκB活化从而下调了TNF α、MIP 2、ICAM 1表达从而减轻中性粒细胞浸润及肝脏缺血再灌注损伤。     

Protective effect of intraperitoneal ozone application in experimental ovarian ischemia/reperfusion injury

AimThe current accepted management of ovarian torsion is ovary-sparing surgery. Ozone therapy is used to reduce ischemia/reperfusion (I/R) injury in several situations. An experimental study was designed to evaluate effect of ozone application in ovarian I/R injury.Materials and methodsThree groups (n = 6) and 18 rats were included in the study. After anesthesia, right ovaries were fixed and removed at the end of 2 hours in sham group (SG). In torsion group (TG), right ovaries underwent 720° torsion in a counterclockwise direction. Ovaries were removed after 2 hours torsion and 2 hours reperfusion. In ozone group (OG), torsion was created by the same technique, and 95% oxygen plus 5% ozone gas mixture was given intraperitoneally (25 μg/mL, 0.5 mg/kg) 10 minutes before reperfusion. After 2 hours reperfusion, ovaries were removed. Histopathologic examination of ovarian and periovarian sections was performed for the presence of congestion (C), hemorrhage, interstitial edema (IE), and polymorphonuclear neutrophilic infiltrations. Tissue samples were analyzed for malondialdehyde, nitric oxide (NO), and total sulphidryl (t-SH) values. Results were compared between 3 groups.ResultsAt histopathologic examination, the TG have elevation in terms of ovarian C, polymorphonuclear neutrophilic infiltration, and periovarian IE when compared with SG (P < ,05). In OG, ovarian C and periovarian IE were reduced according to TG, whereas the increase was observed only in ovarian C compared with SG (P < .05). At biochemical evaluation of oxidative stress markers in SG and TG, there was no difference between them (P < .05). Malondialdehyde levels were significantly lower in OG than TG, whereas NO and t-SH values were higher (P < .05). Malondialdehyde levels were decreased in OG compared with SG (P < .05). However, no difference was observed in NO and t-SH levels (P > .05).ConclusionIntraperitoneal application of ozone creates a positive impact on histologic and biochemical markers on I/R injury owing to ovarian torsion. The ozone application can be developed to support efforts to protect ovary in ovarian torsion.     

山莨菪碱对皮瓣缺血再灌注损伤保护机制的实验研究

目的 观察山莨宕碱注射液对大鼠缺血再灌注皮瓣成活面积及组织学变化的影响,以期证实山莨宕碱具有防治皮瓣坏死、提高皮瓣成活率的疗效.方法 48只大鼠随机分为缺血再灌注盐水组、缺血再灌注山莨宕碱处理组及对照组,建立以腹壁浅血管为蒂的轴型皮瓣,3组大鼠于掀起皮瓣后即刻及掀起皮瓣后12、18、34 h分别于皮瓣中段取材,检测皮瓣组织中超氧化物歧化酶(SOD)、一氧化氮(N0)及核因子NF-κB的含量,显微镜下观察皮瓣组织病理学变化情况,并于术后第7天观测皮瓣成活率.结果 缺血再灌注山莨宕碱处理组皮瓣成活率为(78.6％ ±7.3)％,再灌注后2、8、24 h皮瓣组织中SOD含量为(103.3±3.9)、(82.6±3.8)、(67.5±4.6) U/mg,NO含量为(5.33±2.05)、(4.75±1.68)、(4.15±1.59) nmol/mg,NF-κB含量为0.211±0.039、0.313±0.033、0.096±0.028.3组大鼠皮瓣组织中SOD、NO及NF-κB的含量在不同时刻相比较差异均有统计学意义;山莨宕碱处理组大鼠皮瓣病理变化情况明显好于盐水组;山莨宕碱处理组皮瓣成活率明显高于盐水组.结论 山莨宕碱能够减轻再灌注后皮瓣组织内自由基损伤,增加皮瓣术后血运,减少核因子NF-κB的产生,减轻炎性反应,增强皮瓣抗感染能力,从而可有效减轻皮瓣缺血再灌注损伤,降低皮瓣坏死率,提高皮瓣移植成活率.     

The effects of a specific neutrophil elastase inhibitor (ONO-5046) in pulmonary ischemia–reperfusion injury

Ischemia-reperfusion injury is a significant problem in lung transplantation. Polymorphonuclear elastase derived from neutrophils plays a major mechanistic role in this process. Hence, we have investigated the effects of ONO-5046, a neutrophil elastase inhibitor, on ischemia-reperfusion injury. Fifteen rabbits were divided into three groups: 2 h of single left-lung perfusion (control group, n=3); 2 h of ischemia followed by 2 h of reperfusion (ischemic group, n=6); and drip intravenous administration of ONO-5046 during the 2 h of ischemia and 2 h of reperfusion (ONO-5046 group, n=6). Hemodynamic parameters were determined and a histopathological examination of the lung was performed. In the ONO-5046 group, arterial oxygen pressure, cardiac output, and tissue blood perfusion were higher and pulmonary vascular resistance was lower than in the ischemic group. The ONO-5046 group also showed large decreases in neutrophil infiltration, pulmonary edema, and intra-alveolar hemorrhage. Treatment with ONO-5046 improves lung function in a rabbit-lung ischemia-reperfusion model.     

吡咯烷二巯基氨甲酸对大鼠肾缺血再灌注的保护作用及机制

目的 探讨吡咯烷二巯基氨甲酸(PDTC)对大鼠肾缺血再灌注的保护作用及可能的机制.方法 选择成年、健康及雄性的Wistar大鼠56只,随机分为缺血再灌注损伤(IRI)组,PDTC组及对照组.IRI组:24只,建立大鼠肾缺血再灌注模型;PDTC组:24只,缺血再灌注前15 min经鼠尾静脉注射PDTC 150 mg/kg,其余步骤同IRI组;对照组:8只,不给予缺血再灌注处理.IRI组和PDTC组分别于再灌注后2、6和24 h检测大鼠血清肌酐(Cr)和尿素氮(BUN)水平;检测肾组织中自细胞介素8(IL-8)和肿瘤坏死因子α(TNF-α)的含量;逆转录聚合酶链反应(RT-PCR)检测肾组织中核因子-κB(NF-κB)和诱导型一氧化氮合酶(iNOS)mRNA表达水平;苏木素-伊红(HE)染色观察大鼠肾组织的病理变化.取对照组的各项数据作为正常对照.结果 IRI组大鼠再灌注后各时间点的血Cr、BUN、IL-8及TNF-α含量、NF-κB和iNOS mRNA表达水平均高于对照组和PDTC组(P<0.05).再灌注后6 h时,PDTC组大鼠肾组织中IL-8和TNF-α含量与对照组比较,差异无统计学意义(P>0.05).再灌注后24 h时,PDTC组大鼠各项生化指标与对照组相比,差异均无统计学意义(P>0.05).PDTC组大鼠肾损伤的病理变化较IRI大鼠明显减轻.结论 PDTC通过抑制NF-κB,有效减少IL-8,TNFα和iNOS的产生,对肾缺血再灌注有良好的保护作用.     

Protective effect of erythropoietin on renal ischemia and reperfusion injury

BACKGROUND: Multiple protective effects of erythropoietin (EPO), such as antiapoptotic, antioxidant, angiogenic and neuroprotective effects, against ischemia have been demonstrated in cell culture and animal models. Genistein is also a potent tyrosine kinase inhibitor. The aims of the present study were to evaluate the effects of EPO on renal ischemia/reperfusion injury and to determine the role of the tyrosine kinase pathway on this process. METHODS: Sprague-Dawley rats were assigned to five groups: (i) sham (Group I); (ii) control with renal ischemia (right nephrectomy and clamping on the left renal pedicle for 45 min and reperfusion; Group II); (iii) EPO + ischemia (Group III); (iv) genistein (an inhibitor of tyrosine kinase) + ischemia (Group IV); and (v) EPO + genistein + ischemia (Group V). Recombinant human EPO (1000 IU/kg) and genistein (10 mg/kg) were given 2 hours before ischemia. Blood samples and the left kidney were obtained after 45 min of reperfusion from half of the rats and after 24 h from the other half. RESULTS: The blood urea nitrogen, creatinine, tumour necrosis factor-alpha (P < 0.05) and interleukin-2 (P < 0.01) levels, and renal tissue lipid peroxidation (P < 0.05) were significantly lower in Group III than in Group II at 45 min of reperfusion. Following 24 h of reperfusion, EPO decreased tissue peroxidation and histopathological injury, whereas genistein reversed it. The most prominent ischemic injury was observed in Group IV in which genistein was administered. There was no significant difference between Groups II and V. CONCLUSIONS: These results suggest that EPO is effective in attenuating renal ischemia/reperfusion injury, and this effect may be related to tyrosine kinase activity.     

右美托咪定对脏器缺血/再灌注损伤的保护作用机制

背景 右美托咪定(dexmedetomidine,Dex)是一种新型高选择性α2-肾上腺素受体(alpha-2-adrenergic receptor,α2-AR)激动剂,Dex除具有镇静、镇痛、围术期交感阻滞的作用外,大量的研究表明Dex对多脏器的缺血/再灌注损伤(ischemidreperfusion injury,I/RI)具有保护作用. 目的 综述国内外Dex对多脏器I/RI保护机制的研究进展,为Dex脏器保护机制的研究提供思路. 内容 Dex通过减轻再灌注过程中的氧化应激反应,降低炎性因子的表达,减少机体细胞凋亡,保护红细胞变形能力来发挥脏器保护作用. 趋势 随着Dex对多脏器I/RI的保护机制不断被阐明,将为其临床应用提供更为深入的理论基础.     

氨溴索对大鼠肝脏缺血再灌注损伤的保护作用

目的：探讨氨溴索对大鼠肝脏缺血再灌注损伤（I/RI）的保护作用及其机制。方法：18只雄性Wistar大鼠被随机均分为假手术组、肝I/RI模型组（模型组）、氨溴索预处理+肝I/RI模型组（氨溴索预处理组）。肝I/RI模型采用阻断入肝血流30 min后再灌注方法诱导,氨溴索预处理组于缺血前20 min尾静脉注射氨溴索（100 mg/kg）,而模型组给予等体积生理盐水。术后6 h处死大鼠,检测血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平和肝组织病理学改变,同时检测肝组织超氧化物岐化酶（SOD）,谷胱甘肽（GSH）,丙二醛（MDA）含量,caspase-3的活化水平。结果：与假手术组比较,模型组与氨溴索预处理组血清ALT和AST水平明显升高（均P<0.05）;肝组织出现明显的病理学改变;肝组织SOD和GSH含量明显下降,而MDA水平明显升高（均P<0.05）;肝组织caspase-3活化水平明显升高（均P<0.05）。与模型组比较,氨溴索预处理组以上各项指标的变化均明显减弱（均P<0.05）。结论：氨溴索预处理能减轻大鼠肝脏I/RI,机制可能与其调控抗氧化和抗凋亡信号通路有关。