Expressions of tumor necrosis factor-converting enzyme and ErbB3 in rats with chronic obstructive pulmonary disease

Background Chronic obstructive pulmonary disease (COPD) is associated not only with airway inflammation characterized by mucin hypersecretion but also with systemic inflammation. Tumor necrosis factor alpha (TNF-α) is found to take part in systemic inflammation, and ErbB3 plays an important role in mucin hypersecretion of COPD. Since TNF-α converting enzyme (TACE) is involved in the activation of both TNF-α and ErbB3, we established rat models of COPD to investigate the expressions of TACE, TNF-α and ErbB3 and to explore the correlations among TACE,TNF-α and ErbB3 respectively. Methods Thirty Wistar male rats were randomly divided into COPD group (group C, n=10), saline solution parallel group (group P, n=8), and normal control group (group N, n=8). Group C was challenged with passive cigarette smoking and intratracheal instillation of lipopolysaccharide. Six weeks later pulmonary functions were tested, bronchoalveolar fluid and arterial blood gases were assayed, and histopathological evaluations were performed in turn. The expressions of TACE, TNF-α and ErbB3 in lungs of all rats were determined histochemically. Results The expressions of TACE, TNF-α and ErbB3 were significantly higher in group C than in group N (P<0.01). The contents of TNF-α in serum (P<0.01) and bronchoalveolar lavage fluid (BALF) (P<0.01) were elevated more significantly in group C than in group N. A positive correlation existed between TACE and TNF-α (r=0.784, P<0.01) and between TACE and ErbB3 (r=0.526, P<0.01) respectively. Conclusions TNF-α and ErbB3 are involved in the pathogenesis of COPD. TACE contributes to the progress of COPD indirectly through the function of TNF-α and ErbB3.     

Dynamic changes in blood cytokine levels as clinical indicators in severe acute respiratory syndrome

Objective To investigate the dynamic changes observed in serum levels of interleukins (ILs), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in severe acute respiratory syndrome (SARS) patients.Methods Sixty-one cases of SARS with positive antibodies to SARS coronavirus (SARS-CoV) were classified into the following categories: initial stage (3-7 days), peak stage (8-14 days), and remission and recovery stage (15-27 days). Forty-four healthy individuals were used as controls. Serum levels of ILs, TNF-α and TGF-β1 were measured in all subjects. Serum antibodies to SARS-CoV were detected only in SARS cases. Results The mean concentration of serum IL-6 in SARS patients did not differ from that in the control group in initial and peak stages, but became significantly higher in remission and recovery stage compared with the control group, initial and peak stages (P<0.01). The mean concentration of serum IL-8 in SARS patients did not differ from that of the control group in initial stage, but was significantly higher than control group in peak stage and remission and recovery stage （P<0.05）. And it was more significantly higher in remission and recovery stage than in peak stage （P<0.01）. The mean concentrations of IL-16 and TNF-α in SARS patients were higher than those of the control group for every length of the clinical courses investigated, and were especially high in remission and recovery stage （P<0.01）. SARS patients experienced higher concentration of serum IL-13 compared with the controls in initial stage （P<0.01）, but returned to normal levels in peak stage and in remission and recovery stage. The mean concentration of serum IL-18 in SARS patients was significantly lower than that of the control group during all clinical courses （P<0.05）. The mean concentration of serum TGF-β1 in SARS patients was higher than that of the control group during all clinical courses. Although TGF-β1 in serum decreased in remission and recovery stage in SARS patients, the average was still higher than that of the control group （P<0.01）.Conclusions Most proinflammatory cytokines and TGF-β1 were elevated during the early phase of SARS, which may be associated with lung infiltration and proliferation. Concurrently, the mean concentration of serum IL-13 decreased gradually, and the mean concentration of serum IL-18 level in SARS patients was lower than that of the control group during all the courses of SARS, suggesting that the immune state of the patients with SARS was obviously abnormal. Observing the dynamic changes in blood cytokine levels can provide a scientific basis to assess pathogenesis and efficacy of clinical treatment of SARS.     

Changes in intestinal microflora in patients with chronic severe hepatitis

Objective To investigate changes in intestinal microflora in patients with chronic severe hepatitis (CSH), and their role in this life-threatening disease.Methods We classified nineteen patients with chronic severe hepatitis as the CSH group, thirty patients with chronic hepatitis (CH) as the CH group and thirty-one heal thy volunteer as the control group. Fecal flora from all subjects were analyzed . Concentrations of plasma endotoxin, serum cytokines tumor necrosis factor alp ha (TNF-α) and interleukin-1 beta (IL-1β) and liver function were assessed .Results The number of fecal bifidobacterium (P<0.001, P<0.05 respectively), as well as bacteroidaceae (P<0.001, P<0.01 respectively) were significan tly deceased in patients with chronic severe hepatitis compared with the CH and control groups, while the number of enterobacteriaceae (P<0.001, P< 0.05 respectively) and yeasts (P<0.01, P<0.05 respectively) were sign ificantly increased. Levels of plasma endotoxin, serum TNF-α, IL-1β and tot al bilirubin (TBiL) were significantly increased in the CSH group. The concentr ation of endotoxin positively correlated with levels of both TNF-α, IL-1β an d TBiL (P<0.001, respectively). Levels of plasma endotoxin were positivel y correlated with the number of fecal enterobacteriaceae and negatively correlat ed with bifidobacterium (P<0.05, P<0.001, respectively).Conclusion Intestinal flora in patients with chronic severe hepatitis were severely disturb ed and gut mircobiological colonization resistance was impaired. Changes in int estinal flora may have a pivotal role in both the elevation of plasma endotoxin and further hepatic lesions resulting in liver failure.     

Chronic blocking of β3-adrenoceptor ameliorates cardiac function in rat model of heart failure

Background Stimulation of the heart β(3)-adrenoceptor (AR) may result in a negative inotropic effect. Being up-regulated, β(3)-AR plays a more important role in the regulation of cardiac function during heart failure. However, the effect of chronic blocking of β(3)-AR on heart failure has not been fully elucidated. In this study, we used a selective β(3)-AR antagonist SR59230A to treat a well defined heart failure rat model chronically, then evaluated its effect on cardiac function and investigated the mechanism.Methods Male Wistar rats were chosen randomly as controls (n=8). Isoproterenol induced heart failure rats were randomly divided into ISO group (n=10) and SR group (n=10). The ISO group received intraperitoneal injection of 1 ml saline twice a day; the SR group received intraperitoneal injection of SR59230A 85 nmol in 1 ml saline twice a day; and the control group received no treatment. The treatment was started 24 hours after the last isoproterenol injection and continued for 7 weeks. Then we measured the following indexes: the ratio of heart weight to body weight (HW/BW) and the ratio of left ventricular weight to body weight (LVW/BW), collagen volume fraction (CVF), left ventricular end diastolic dimension (LVEDd), left ventricular end systolic dimension (LVESd), ejection fraction (EF), fractional shortening (FS) and the ratio of E wave to A wave (E/A),the mRNA and protein expression of β(3)-AR and eNOS, and cGMP level in the heart.Results The ratios HW/BW and LVW/BW were significantly increased in the ISO group compared with the control group (P<0.01), but they were limited in the SR group (P<0.05 compared with the ISO group). CVF increased in the ISO group and the SR group (P<0.01), but it was significantly attenuated in the SR group (P<0.01). LVEDd, LVESd and E/A ratio were significantly increased in the ISO group compared with the control group (P<0.01), while EF and FS were significantly decreased (P<0.01). Compared with the ISO group, the SR group showed that LVEDd, LVESd and E/A ratio were significantly decreased (P<0.01), whereas EF and FS were significantly increased (P<0.01). β(3)-AR and eNOS mRNA and protein in the ISO group were significantly increased when compared with the control group (P<0.01). These increases were all attenuated in the SR group compared with the ISO group (P<0.01). The level of cGMP in myocardial tissue was significantly increased in the ISO group compared with the control group (P<0.01), whereas SR59230A treatment normalized this increment (P<0.01).Conclusions Chronic blocking of β(3)-AR could ameliorate cardiac function in heart failure rats and its mechanism involves inhibition of the negative inotropic effect and attenuation of cardiac remodeling.     

Effects of glycine and methylprednisolone on hemorrhagic shock in rats

Background Methylprednisolone (MP), a synthetic glucocorticosteroid, has been broadly studied in experiments on endotoxin-induced shock and septic shock. This study was designed to ascertain whether glycine and MP can protect against organ injury and death caused by hemorrhagic shock, and to elucidate the underlying mechanisms of these protective effects in rats.Method To establish a shock model, Wistar rats were bled to maintain mean arterial pressure at 30-50 mmHg for 1 hour and subsequently resuscitated with the shed blood and normal saline. Just prior to resuscitation, the rats were randomly assigned to four groups: sham group (operation performed without inducing shock), shock group, shock+glycine group (glycine injected at the beginning of resuscitation) and shock+MP group (MP injected at the beginning of resuscitation).Results ① Seventy-two hours after resuscitation, the survival rate of rats from the shock group had decreased to 20%, while the survival rates of rats from the shock+glycine and shock+MP groups were 77.8% and 80%, respectively. The difference was significant (P<0.05). ② Eighteen hours after resuscitation, pathological alterations in the organs of the rats were apparent. In rats from the shock group, edema, interstitial leukocyte infiltration, and cellular degeneration occurred in the liver, lungs, kidneys, and heart. Glycine and MP reduced these pathological changes significantly. ③ Eighteen hours after resuscitation, the levels of creatine phosphokinase, transaminases, and creatine were elevated significantly in rats from the shock group, indicating injury to the heart, liver, and kidneys, while these levels were elevated only slightly in the shock+glycine and shock+MP groups. The differences were significant (P<0.01). ④ There were significant increases in intracellular calcium and production of tumor necrosis factor (TNF-α) by isolated Kupffer cells stimulated by endotoxin after hemorrhagic shock. These changes were completely prevented by glycine and MP (P<0.01). Conclusion Glycine and MP reduce organ injury and mortality caused by hemorrhagic shock by preventing increase of intracellular calcium levels in Kupffer cell, suppressing Kupffer cell activation, decreasing the production of TNF-α by Kupffer cells, and blocking systemic inflammatory responses.     

Effect of glucocorticoid treatment on insulin like growth factor-Ⅰ and its binding proteins in children with nephrotic syndrome

Objective To identify the changes in serum insulin like growth factor-Ⅰ (IGF-Ⅰ) and IGF binding proteins (IGFBPs) in children with nephrotic syndrome (NS) and the effect of glucocorticoid on serum IGF-Ⅰ and IGFBPs. Methods We measured serum IGF-Ⅰ and IGFBPs levels by radioimmune assay and immune radiomagnetic assay in 36 children with NS, consisting of an active stage group (ANS, n=12), a remission stage group (RE, n=12), an active stage group with glucocorticoid treatment (GNS, n=12), and a normal control group (NC, n=10). Results 1) Compared to NC, serum levels of IGF-Ⅰ and IGFBP-3 were decreased (P<0.01); serum levels of IGFBP-1 and IGFBP-2 were increased (P<0.01) in the ANS group. 2) Serum levels of IGF-Ⅰ and IGFBP-3 were higher and IGFBP-1 and IGFBP-2 were lower in the RE Group than in theANS Group (P<0.01). 3) Compared to the ANS group, serum levels of IGF-Ⅰ and IGFBP-3 were increased (P<0.01) and serum levels of IGFBP-1 and IGFBP-2 were decreased (P<0.01) in the GNS group. 4) A correlation was found between serum levels of IGFBP-3 and albumin in the active stage group (r=0.76 P<0.01). There was also a correlation between serum levels of IGF-Ⅰ and IGFBP-3 and an inverse correlation between the serum level of IGF-Ⅰ and serum levels of IGFBP-1 and IGFBP-2 in the ANS group. No other correlations were observed.Conclusions The serum levels of IGF-Ⅰ and IGFBPs are altered in children in the active stage of NS, but return to normal in the remission stage. GC treatment may influence serum IGF-Ⅰ and IGFBPs in children with NS. Changes in IGF-Ⅰ and IGFBPs levels may play a role in the growth retardation of NS children.     

电针ST36穴位治疗牛黄胆酸钠诱导的急性重症胰腺炎的疗效观察

Objective:To explore the protective effects and mechanisms of electroacupuncture(EA)at Zusanli(ST36)acupoint in rats with severe acute pancreatitis(SAP).Methods:Sixty-six male SpragueDawley rats were randomly assigned to three groups of 22 each:a SAP model group(SAP group),a shamoperated group(sham group)and a EA at ST36 acupoint group(EA group).A rat model of SAP was induced by pancreatic duct injection with 3.5%sodium taurocholate.EA was performed at ST36 acupoint for 30 min after induction of SAP and 30 min before sacrificed.The rats were killed at 3 h(n=7),6 h(n=7)and 12 h(n=8)after operation,and blood samples were taken for the measurement of tumor necrosis factor-alpha(TNF-a),interleukin-6(IL-6)and acetylcholine(Ach)by enzyme-linked immunosorbnent assay.The pathological changes of pancreatic tissue,volume of ascites and pancreatic weight/body weight ratio were measured.Results:The serum concentrations of TNF-αand IL-6 in the EA group were significantly lower than in the SAP group at 3,6and 12 h after the operation(P0.05).Serum Ach in the EA group was significantly higher than in the SAP group at various time points after operation(P0.05).The other parameters were clearly improved after treatment with EA.Conclusion:EA at ST36 acupoint might have a therapeutic effect in rats with SAP through activating the cholinergic anti-inflammatory pathway.     

Effects of mycophenolate mofetil, valsartan and their combined therapy on preventing podocyte loss in early stage of diabetic nephropathy in rats

Background Podocyte has inflammatory role in the development of diabetic nephropathy (DN). Mycophenolate mofetil (MMF), an anti-inflammatory agent, can suppress macrophage infiltration and reduce renal injury in streptozotocin-induced diabetic rats. Angiotensin II receptor blocker (ARB), another renal protecting agent, can decrease podocyte loss in DN. In this study, we detected the expression levels of monocyte chemoattractant protein-1 (MCP-1) and nephrin to evaluate podocyte’s role in inflammatory reaction in DN, observe and compare the effect of MMF alone and in combination with valsartan, on preventing podocyte loss in streptozotocin (STZ) induced diabetic rats. Methods Diabetic model was constructed in uninephrectomized male Wistar rats by single peritoneal injection of STZ (65 mg/kg). The successfully induced diabetic rats were randomly divided into four groups: diabetes without treatment group (DM), valsartan treated group (DMV), MMF treated group (DMM), and combined therapy group (DMVM). Normal rats of the same sibling were chosen as control (NC). At the end of the 8th week, serum biochemistry, 24-hour urinary protein (UP) and the ratio of kidney weight/body weight (RWK/B) were measured. The rats were sacrificed for the observation of renal histomorphology through light and electron microscope. Nephrin, desmin and MCP-1 levels were detected by semi-quantitative immunohistochemical assays. Real-time quantitative PCR was used to detect the mRNA levels of nephrin and MCP-1.Results Compared with group NC, serum glucose level, 24-hour UP and RWK/B in group DM were significantly higher (P<0.01), and the nephrin mRNA level in DM group was significantly lower (P<0.05). The nephrin mRNA expression levels in group DMV, DMM and DMVM were all higher than that of DM group (P<0.05) and no significant differences were found among the three treatment groups (P>0.05). Treatment with MMF, valsartan or their combination could significantly decrease the 24-hour UP and RWK/B, and suppress glomerulosclerosis and interstitial fibrotic lesions in diabetic rats. In diabetic rats, the high expressions of desmin and MCP-1 in kidney were suppressed by valsartan, MMF or their combination.Conclusions Podocytes are involved in the inflammatory reaction of diabetic rats. MMF could suppress MCP-1 and desmin expression, enhance nephrin expression, and attenuate proteinuria in diabetic rats. The combined therapy of valsartan and MMF did not show any superiority over monotherapies on renal protection. MMF may have renoprotective effect in early stages of diabetic nephropathy through preventing podocytes loss and anti-inflammatory activity.     

Chronic treatment of enbrel in rats with isoproterenol- induced congestive heart failure limits left ventricular dysfunction and remodeling

Objective To investigate the effect of chronic treatment of enbrel (EB), a TNF- α antagonist, in a well defined congestive heart failure (CHF) rat model and test the hypothesis that chronic treatment of EB in CHF rats may limit the progression of Left ventricular (LV) dysfunction and structure remodeling and decrease cardiac IL- 1β levels. Methods We measured cardiac conformation, contractile performance and cytokines level in 8 age- matched normal adult rats (control group) and 8 rats with isoproterenol (ISO)- induced Heart failure (ISO group) and 8 rats with ISO- induced lesion but received EB treatment (EB group). Results LV end diastolic diameter and LV end systolic diameter in EB group were significantly less and LV fractional shortening was significantly larger than ISO group (9. 2±0. 3 mm vs 9. 5±0. 2 mm, 5. 8±0. 5 mm vs 6. 5±0. 3 mm, 0. 37±0. 03 vs 0. 31±0. 02,P<0. 05,P<0. 01,P<0. 01 respectively）, but there was no significant difference of LV posterior wall thickness at end diastole between the two groups; LV end systolic pressure (P ES ), dp/dt max in EB group were significantly greater than ISO group (104. 8±4. 6 mm Hg vs 98. 4±4. 9 mm Hg, 8395±940 mm Hg/s vs 6898±612 mm Hg,P<0. 05,P<0. 01 respectively), and LV end diastolic pressure (P ED ), dp/dt min , time constant of LV relaxation were significantly lower than ISO group (3. 8±0. 6 mm Hg vs 7. 1±0. 8 mm Hg, -5963±475 mm Hg/s vs -5030±316 mm Hg/s, 15. 4±0. 8 ms vs 21. 3±1. 4 ms,P<0. 01, respectively）. Although cardiac contractile performance in the EB group was greatly improved, there still was a big gap when compared with the control group. The ratio of LV weight to body weight in the EB group was significantly higher than control group （2. 82±0. 07 mg/g vs 2. 28±0. 08 mg/g,P<0. 01）, but there was no significant difference when compared with the ISO group. There was no significant difference between the serum level of TNF- α in EB group and ISO group, the it could not be detected in control group. TNF- α levels in LV of EB group was significantly higher than control group, （757. 6±46. 8 pg/g vs 367. 5±22. 7 pg/g,P<0. 01）, but there was no significant difference when compared with ISO group. The IL- 1β level in LV of EB group was significantly lower than ISO group （356. 2±28. 5 pg/g vs 518. 4±32. 5 pg/g,P<0. 05）, and it could not be detected in control group. The serum level of IL- 1β could not be detected in any rats. Conclusion EB administered as soon as possible when ISO induced myocardial necrosis occurs can greatly improve cardiac contraction, and the improvement may be partly due to a decrease in the IL- 1β level in LV, besides the direct blocking effect of EB on TNF- α. EB can alleviate cardiac remodeling by its effect on LVEDD.      

Effect of propentofylline on hypoxic-ischaemic brain damage in newborn rat

Background Studies showed that propentofylline enhances the action of adenosine and protects hippocampal neuronal demage against transient global cerebral ischaemia. Our study was to investigate the effect of propentofylline on hypoxic-ischaemic brain damage in neonatal rat.Methods Seven-day-old Wistar rats were subjected to unilateral common carotid artery ligation and hypoxia in oxygen 8 kPa for two hours at 37℃. Propentofylline (10 mg/kg) was administered intraperitoneally one hour after hypoxia-ischaemia (treated group). Control group rats were received an equivalent volume of saline. The effects of propentofylline were assessed by observing the body mass gain, behavioural alteration and neurohistological changes. The rats were sacrificed at 72 hours after hypoxia-ischaemia, and the brain sections were examined after haematoxylin and eosin staining.Results The propentofylline-treated rats had better body mass gain and better behavioural response than the paired saline-controls did. In the control group, the rats either lost body mass or had little mass gain after the insult, their average body mass gain was 97.3% at 24 h, 100.3% at 48 h, and 114.1% at 72 h of recovery. In propentofylline-treated group, there was a significant improvement of body mass gain at 24 h (100.2%, P<0.05) and 48 h (110.3%, P<0.01) of recovery; the percentage of rats that performed well on behavioural test was significantly higher from 48 h to 72 h of recovery (P<0.05); the incidence of severe brain damage to the cerebral cortex and dentate gyrus was significantly reduced in propentofylline-treated rats (cortex, 93%-70.8%, P<0.01; dentate gyrus 95%-66.7%, P<0.01) as compared with control rats. Conclusions Administration of propentofylline 1 hour after hypoxia-ischaemia significantly attenuates brain damage in both the cerebral cortex and dentate gyrus, and also improves the body mass gain as well as behavioural disturbance in 7-day-old rats.     

小剂量低分子肝素对重症急性胰腺炎大鼠胰腺微循环的影响

目的:探讨小剂量低分子肝素对重症急性胰腺炎(SAP)大鼠胰腺微循环血流及血管通透性的影响。方法:逆行经胰胆管注入3%牛磺胆酸钠诱导致大鼠重症胰腺炎模型,于不同时相给予低分子肝素(LMWH)处理并观察胰腺微循环血流及测定微血管通透性,进行病理评分。结果:早期应用低分子肝素能改善重症胰腺炎大鼠胰腺微循环。结论:低分子肝素是改善重症胰腺炎胰腺微循环的有效途径。     

早期区域动脉灌注微量低分子肝素改善高脂血症性急性胰腺炎微循环的实验研究

目的 观察早期微量低分子肝素(LMWH)区域动脉灌注(LAI)后对高脂血症性急性胰腺炎(HLAP)仓鼠模型微循环及病情的影响.方法 健康成年雄性仓鼠共30只,随机均分为3组:区域动脉输注生理盐水组(LAI + saline组)、区域动脉输注低分子肝素组(LAI + LMWH组)和静脉输注低分子肝素组(IV + LMWH组).每组予以高脂饲料(20％猪油+ 10％胆固醇+ 1％丙基硫氧嘧啶+ 1％胆酸钠+ 68. 9％普通饲料)喂养.4周造模成功后,按照Schimidt法,于造模后 30 min 时 LAI + LMWH 组注入 LMWH 20 IU/kg,IV+ LMWH组经静脉输注等量的LMWH,LAI + saline组采取与LAI + LMWH组相同的输注方式注入等容量生理盐水.所有动物造模前经外周静脉注入吖啶橙靶向白细胞荧光染料(2 ml/kg),注射完毕后以激光共聚焦显微镜荧光成像系统动态观察活体动物胰腺微循环,分别于造模前、造模后4 h及6 h 3个时间点检测胰腺微循环血管平均直径(MVD)、功能性毛细血管密度(FCD)及微循环血流速度(MFV)、白细胞黏附水平.6 h后抽取静脉血测定血三酰甘油及血淀粉酶水平,然后处死动物获取胰腺组织,并观察病理学改变,记录胰腺病理学评分.结果 灌注LMWH4 h后的LAI + LMWH组与 IV + LMWH 组及 LAI + saline 组比较,LAI + LMWH 组的胰腺微循环功能指标MVD、FCD、MFV呈显著上升趋势(P<0.05),白细胞黏附数呈明显下降趋势(P<0.05);灌注 LMWH 6 h 后的 LAI + LMWH 组与 IV + LMWH 组及 LAI + saline组比较,LAI +LMWH组的胰腺微循环功能指标MVD、 FCD、MFV呈缓慢上升趋势(P<0. 05),白细胞黏附数呈缓慢下降趋势(P<0. 05),IV + LMWH组与LAI + saline组相比差异无统计学意义;除灌注生理盐水组外,其余各组的胰腺病理学评分较灌注前均有明显改善,4 h时的LAI + LMWH 组改善最显著,6 h时的LAI + LMWH组次之.结论早期区域动脉灌注微量LMWH能明显改善HLAP仓鼠模型微循环功能障碍和病情,对HLAP有显著的治疗作用.     

硫化氢与大鼠急性重症胰腺炎相关性的实验研究

目的探讨硫化氢（H2S）对大鼠急性重症胰腺炎（SAP）组织损伤的影响。方法健康雄性大鼠160只,大鼠随机分四组：对照组,n=40;SAP组,n=40;SAP＋硫氢化钠（NaHS）组,n=40;SAP＋DL-炔丙基甘氨酸（PAG）组,n=40。每组随机分为四小组,分别对应末次注射L—Arg后3h、12h、24h、36h四个时间点,每小组n=10。分别测定血清H2S、淀粉酶、胰腺组织中胱硫醚-γ-裂解酶（Cystathionine-γ-synthase,CSE）含量、组织病理形态学变化。结果SAP＋NariS组血清淀粉酶较SAP组有显著升高;CSE表达与SAP组无显著性差异;镜下见比SAP组更早出现坏死和小叶结构破坏。SAP＋PAG组与SAP组对照发现,预先腹腔注射PAG后,血清淀粉酶、H2S含量及组织CSE含量明显降低,其差异有显著性,病理结果显示,显著延缓了胰腺组织损伤的出现,出血、炎症细胞浸润明显减少,Grewal胰腺病理损伤评估证实与SAP组有显著差异。结论血清H2S含量与组织损伤呈正相关,PAG有减轻大鼠胰腺炎模型胰腺组织的损伤作用。     

重症急性胰腺炎急性期细胞因子及胰腺腺泡细胞凋亡的动态变化

目的 本研究通过重症急性胰腺炎（SAP）大鼠血清淀粉酶、TNFa、IL－6、胰腺腺泡细胞凋亡指数及胰腺组织学变化程度作用的动态观察，以进一步了解治疗SAP的作用机理。方法 用chetty法制做大鼠SAP模型，动态测定术后0h、24h、30h、36h各组血清TNFa、IL－6浓度，并取得胰组织做病理学检查；同时，应用TUNEL技术分析大鼠胰腺腺泡细胞凋亡的变化。结果 研究发现SAP组30、36h时血清TNFa、IL－6水平明显升高，腹水量明显增加，胰组织病变程度明显加重；胰腺腺泡细胞凋亡指数较SAP组胰腺腺泡细胞凋亡指数明显升高。结论 重症急性胰腺炎（SAP）胰酶及炎症介质的释放及胰腺腺泡细胞凋亡在其病情发展起一定的作用。     

柴芩承气汤对重症急性胰腺炎大鼠胆碱能抗炎通路的影响

目的探讨重症急性胰腺炎（SAP）大鼠血清乙酰胆碱酯酶（true choline esterase，TChE）和乙酰胆碱转移酶（choline acetyltransferase。ChAT）的变化及其与IL-6和TNF-α相关性以及柴芩承气汤（Chai Qin Cheng Qi Decoction，CQCQD）对其的影响。方法将30只SD大鼠随机分成3组（假模手术型组、SAP组和CQCQD治疗组），每组10只。检测各组血生化指标、淀粉酶、TNF-α、IL-6、TChE及ChAT。结果SAP组较假手术模型组血清IL-6、TNF-α及TChE升高（P〈0．01），血清ChAT降低（P〈0．01）；血清IL-6与TChE呈正相关（r=0．95，P=0．000），与ChAT呈负相关（r=0．91，P=0．000）；TNF-α与TChE呈正相关（r=0．93，P=0．000），与ChAT呈负相关（r=-0．95，P=0．004）。CQCQD治疗组血清IL-6、TNF-α较SAP组低（P〈0．01），血清ChAT较SAP组高（P〈0．01）。假手术模型组、CQCQD治疗组和SAP组WBC、ALT、AST及LDH依次升高（P〈0．01）。结论胆碱能抗炎通路在SAP大鼠的病理生理过程中起着重要作用。柴芩承气汤可通过影响其功能．减轻全身炎性反应综合征，减少脏器功能受损。     

谷氨酰胺对重症胰腺炎大鼠血清细胞因子水平的影响

目的探讨谷氨酰胺对重症急性胰腺炎大鼠TNF—a、IL-6、IL-10水平的影响。方法54只大鼠分3组：谷氨酰胺（Gln）治疗组,重症胰腺炎（SAP）组,对照（NC）组,每组18只。顺行穿刺注射4％牛磺胆酸钠制作SAP模型。Gin组自阴茎背静脉注射Gin,SAP组与NC组注射生理盐水。比较3组3、6、12h腹水量,血清淀粉酶水平,细胞因子水平及组织病理学评分。结果SAP组腹水、血清淀粉酶、病理学评分、TNF—a,IL-6与NC组各时段比较均升高,差异有统计学意义;IL-10水平在3h较NC组升高,差异有统计学意义（P〈0．05）。Gln组腹水、血清淀粉酶、病理学评分3h和6h时段均较SAP组降低,差异有统计学意义（P〈0．05）;TNF—a,IL-6水平较SAP组各时段均降低,差异有统计学意义（P〈0．05）;IL-10水平3h低于SAP组,差异有统计学意义（P〈0．05）,6h和12h无显著变化。结论谷氨酰胺可调节细胞因子水平,减轻胰腺组织的病理学损害,对SAP有治疗作用。     

HMGB1、TLR4在重症急性胰腺炎大鼠胰腺组织中的表达及乌司他丁的干预效应

目的：探讨 HMGB1、TLR4在重症急性胰腺炎大鼠胰腺组织中的作用机制以及乌司他丁的干预效应。方法将54只SD大鼠分为对照组、SAP组和乌司他丁治疗组,3组又分为6、12 h和24 h 3个小组（每小组n＝6）。对照组开腹后仅翻动胰腺组织,SAP组用5％的牛磺胆酸钠制备SAP模型,治疗组在SAP造模成功后经尾静脉注射乌司他丁。观察3组大鼠胰腺组织的病理学改变;EPS‐G7法检测血清中的淀粉酶;ELISA法检测血清及胰腺组织中的HMGB1;Envision两步免疫法检测胰腺组织中的HMGB1、TLR4的表达水平。结果 SAP组、治疗组各时间点的淀粉酶与对照组比较明显升高,病理学改变明显,差异均有统计学意义（P＜0．05）,示SAP造模成功;SAP组在胰腺组织及血清中的 HMGB1表达在6 h开始升高,于12 h快速上升,至24 h保持上升趋势,与对照组大鼠相同时间点比较明显升高,差异有统计学意义（P＜0．05）,治疗组与SAP组相同时间点的 HMGB1比较明显降低,差异有统计学意义（P＜0．05）;SAP组胰腺组织中的 TLR4表达在6 h开始升高,12 h达高峰,24 h开始下降,与对照组大鼠相同时间点比较明显升高,差异有统计学意义（P＜0．05）。治疗组与SAP组相同时间点的TLR4比较明显降低,差异有统计学意义（P＜0．05）。结论 HMGB1在SAP大鼠胰腺中的致炎作用可能是部分结合其受体 TLR4并通过MyD88依赖性途径而实现的,而乌司他丁可能是通过中断SAP大鼠胰腺组织中的 HMGB1、TLR4信号通路发挥保护作用。     

促红细胞生成素预处理对重症急性胰腺炎促炎抗炎失衡的影响

目的评估促红细胞生成素(EPO)预处理对重症急性胰腺炎促炎抗炎失衡的干预效果及探讨其可能机制。方法健康雄性SD大鼠随机分成3组:假手术(SO)组、重症急性胰腺炎(SAP)组和EPO预处理组,每组各30只。SAP组和EPO组建立逆行胆胰管注射3.5%牛黄胆酸钠法(1 ml/kg)SAP模型,EPO组建模前1 h予静脉注射促红细胞生成素(3000 U/kg,1000 U/ml),而SO组和SAP组予静脉注射等体积生理盐水。术后第1、3、6、12、24小时取血清和胰腺标本。检测血清淀粉酶活性;ELISA法检测血清IL-18水平,放射免疫法检测血清IL-10水平。免疫荧光法检测胰腺组织核因子-kappaB转运激活情况;胰腺组织石蜡切片HE染色,进行胰腺病理学评分。结果与SAP组相应时点比较,EPO组核因子-kappaB激活率(除12 h外)显著降低(P<0.05);血清淀粉酶活性显著降低,3、6、12 h(P<0.05);血清IL-18水平显著降低,3、6、24 h(P<0.05),血清IL-10水平无明显降低;病理总评分降低,6、12、24 h(P<0.05)。结论 EPO预处理可通过抑制核因子-kappaB激活,减少促炎细胞因子产生,而对抗炎细胞因子影响不明显,进而调控促炎-抗炎失衡状态,改善SAP病情。     

添加低聚半乳糖肠内营养对重症急性胰腺炎大鼠炎性细胞因子的作用

目的 研究给予添加低聚半乳糖(GOS)肠内营养对重症急性胰腺炎(SAP)大鼠血清炎性细胞因子的作用.方法 将SAP造模成功的32只SD大鼠随机分为普通肠内营养(EN)组(n=16)和GOS-EN组(N=16),同时设立假手术对照组(n=16),然后按照动物处死时间每组又分为4 d和7 d两个时间点亚组,每个亚组各8只动物.采用胰被膜下均匀注射38 g/L牛磺胆酸钠法建立SAP大鼠模型,检测各时间点血清淀粉酶、血清促炎细胞因子TNF-α和抗炎细胞因子IL-2、IL-10水平.结果 各SAP组的血清淀粉酶水平显著高于假手术对照组(P<0.01),GOS-EN组显著低于EN组(P<0.01);各SAP组的TNF-α和IL-10水平均显著高于假手术对照组(P<0.01),而IL-2显著低于假手术对照组(P<0.01).GOS-EN组的TNF-α水平显著低于EN组(P<0.05),而IL-2、IL-10水平以及IL-10/TNF-α比值显著高于EN组(P<0.05).结论 早期给予GOS-EN能够调节SAP大鼠促、抗炎细胞因子平衡.     

三七总皂苷对重症急性胰腺炎大鼠血清中炎症因子的影响

目的：探讨三七总皂苷（PNS）对重症急性胰腺炎（SAP）大鼠血清肿瘤坏死因子（TNF）α、白细胞介素（IL）6、IL-10水平的影响,为其治疗SAP提供理论基础。方法：SD大鼠随机分为假手术组、SAP组、PNS治疗组,每组30只。各组在术后6、12、24h检测血清淀粉酶、TNF-α、IL-6和IL-10水平,观察胰腺病理改变及各组术后48h死亡率。结果：SAP组各时间点血清淀粉酶、TNF-α、IL-6和IL-10水平均显著高于假手术组（P〈0.01）;PNS治疗组各时间点血清淀粉酶、TNF-α和IL-6显著低于SAP组（P〈0.05）,而IL-10水平显著高于SAP组（P〈0.05）;PNS治疗组胰腺组织损害较SAP组减轻（P〈0.01）;假手术组和治疗组48h死亡率显著低于SAP组（P〈0.05）。结论：PNS可减少促炎细胞因子TNF-α、IL-6产生,上调抗炎细胞因子IL-10,从而达到治疗SAP的目的。