西维来司钠对大鼠重症急性胰腺炎后急性肝损伤的保护作用

Protective Effects of Sivelestat on Acute Liver Injury after Severe Acute Pancreatitis in Rats

目的:探讨西维来司钠对大鼠重症急性胰腺炎(SAP)后急性肝损伤的治疗价值。方法:SD大鼠54只随机分为3组,A组为对照组,仅开腹,轻翻动胰腺,B组采用经十二指肠乳头逆行胆胰管注射3.5%牛磺胆酸钠的方法制备大鼠SAP模型,C组为西维来司钠药物治疗组,在制备SAP大鼠模型后微量泵持续静脉滴注西维来司钠;各组又分为3h、6h、12h3个亚组,每时间点6只。检测血浆白介素-6(IL-6)、中性粒细胞弹性蛋白酶(NE)、淀粉酶(AMY)及肝组织匀浆中超氧化物歧化酶(SOD)、丙二醛(MDA)的水平并观察肝、胰病理变化。结果(:1)B组IL-6、NE、AMY、MDA较A组明显升高(P<0.05),SOD明显降低(P<0.05),镜下可见胰腺水肿、炎细胞浸润、坏死,肝脏肝窦充血、细胞浊肿及坏死,且损伤程度随时限延长而加重。(2)C组较B组血浆IL-6、NE、AMY(12h)及肝组织匀浆中MDA水平下降(P<0.05),SOD升高(P<0.05),胰、肝病理损害程度减轻。结论:西维来司钠通过抑制NE的活性及在肝组织中的表达,抑制SAP急性期炎症反应及有效提高机体对氧自由基的清除能力,减轻SAP致肝损伤的程度。

Objective：To study the role of Sivelestat in the hepatic injury in rats with severe acute pancreatitis（SAP）.Methods：Fifty-four SD rats were randomly divided into three groups,control group（group A）,severe acute pancreatitis group（group B） and treatment with Sivelestat group（group C）.Each group was subdivided into 3 h,6 h and 12 h subgroups（n=6 in each subgroup）.Rats of group A were only operated with a celiotomy.SAP was induced by retrograde injection of 3.5% sodium taurocholate into biliopancreatic duct in group B.Sivelestat was instilled continuously into right jugular vein with infusion pump in group C.The levels of serum interleukin-6（IL-6）,neutrophil elastase（NE） and amylase（AMY） were measured.And the levels of superoxide dismutase（SOD） and malondialdehyde（MDA） in hepatic tissue were also measured.The pathological changes of hepatic and pancreatic tissues were observed by HE staining.Results：（1）The levels of IL-6,NE,AMY and MDA increased significantly（P 0.05）,and SOD significantly decreased（P 0.05）in group B than those of group A.There were pancreatic edema,inflammatory cell infiltration,necrosis,liver sinusoidal congestion,cloudy swelling and necrosis of cells under microscopy.The injury aggravated with time extended.（2）The serum levels of IL-6,NE and AMY,and the level of MDA in liver tissue,decreased significantly in group C than those of group B（P 0.05）,but the level of SOD increased significantly.There was a reduced degree of liver damage in group C.Conclusion：The level of NE was inhibited by treatment with Sivelestat,which could markedly attenuate the hepatic injury in SAP by effectively enhancing the oxygen free radical scavenging capacity and inhibiting inflammatory reaction.