洛沙坦对缺血再灌注大鼠胰腺氧自由基、细胞凋亡和Bcl-2表达的影响

目的： 探讨洛沙坦（losartan）对大鼠胰腺缺血再灌注（I/R）损伤的保护作用及机制。方法：SD大鼠72只随机分为假手术组、I/R组和Losartan组，每组24只。采用钳闭大鼠腹腔干、肠系膜上动脉15,30,60min，再灌注6h，制成胰腺I／R损伤模型。losartan组给予losartan(40mg/kg)灌胃预处理；假手术组和I/R给予等容积的无菌蒸馏水。3组均于术后6ｈ断颈处死动物。用TUNEL法检测I/R区胰腺细胞凋亡、免疫组化法检测Bcl-2蛋白的表达, 并观察胰腺组织病理改变。结果：losartan可逆转胰腺组织炎症细胞浸润、腺泡萎缩等异常改变。缺血15,30min时段，losartan组胰腺细胞凋亡率为（6.5±2.9）％和（10.5±4.3）％显著低于I/R组的（10.2±3.2）％和（18.4±3.1）％（P<0.05）；丙二醛水平为（17.9±2.1）nmol/g（湿重）和（25.2±3.3）nmol/g（湿重）显著低于I/R组的（20.1±1.2）nmol/g（湿重）和（34.9±2.6）nmol/g（湿重）（P<0.05）；Bcl-2阳性细胞为（11.3±2.2）％和（16.2±2.7）％显著高于I/R组的（6.1±1.7）％和（10.3±2.1）％（P<0.05）。结论： losartan可减轻I/R对大鼠胰腺病理改变、抑制细胞凋亡。

Effects of losartan on oxygen free radicals, cell apoptosis and Bcl-2 expression in ischemia-reperfusion injury of pancreas in rats

Abstract:Objective：To investigate the protective effect of losartan on acute ischemia-reperfusion(I/R) injury of pancreas in rats. Methods：Seventy-two Wister rats were randomly divided into 3 groups:（1）Control group;（2）Ischemia-reperfusion group:the anterior mesenteric artery and the celiac artery were occluded for 15 min,30min and 60min followed by 6 hours reperfusion;（3）Losartan group:losartan（40mg／kg）were administered by gavage at 12h and 1h before arterial occlusion. The pathologic changes of pancreatic tissue were observed under light microscopy; TUNEL was used to detect apoptosic of pancreatic cells;Bcl-2 expression in the pancreatic cells of rats was analyzed by immunohistochemistry technique. Results：Losartan treatment reversed the histological abnormalities including infiltration of inflammatory cells and atrophy of acinar cells.Compared with losartan group,pancreatic tissue of I/R group exhibited increased MDA［（20.1±1.2）nmol/g and （34.9±2.6） vs（17.9±2.1）nmol/g and （25.2±3.3）nmol/g,P<0.05］ and apoptosis［（10.2±3.2）％ and （18.4±3.1）％ vs. （6.5±2.9）％ and （10.5±4.3）％,P<0.05］.The administration of losartan increased expression of Bcl-2（11.3±2.2）％ and （16.2±2.7）％ vs （6.1±1.7）％、（10.3±2.1）％，P<0.05）.Conclusions：Losartan can decrease the pathologic changes and suppress cell apoptosis in pancreas of rats with I/R.