氯沙坦保护大鼠胰腺缺血/再灌注损伤作用的机制探讨

Research on Mechanism of Angiotensin Ⅱ Type Ⅰ Receptor Antagonist's Effects in Protecting Rats in Pancreatic Ischemia-Reperfusion Injury

【目的】探讨氯沙坦(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90只随机分为假手术组、I/R组和氯沙坦(Losartan)组,每组30只。一部分胰组织用于凋亡和免疫组织化学(免疫组化)检测;另一部分准备丙二醛(MDA)测定。【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 min时段,30 min时段,Losartan组胰腺细胞凋亡率为(5.44±0.93)%和(7.70±1.09)%显著低于I/R组的(10.27±1.35)%和(18.59±1.02)%(P<0.05);MDA水平为(16.59±1.04)nmol/g(湿重)和(26.96±1.51)nmol/g(湿重)显著低于I/R组的(20.10±0.69)nmol/g(湿重)和(35.91±1.6)nmol/g(湿重)(P<0.05);Bcl-2阳性细胞为(12.48±0.90)%和(17.73±0.78)%显著高于I/R组的(6.56±0.58)%和(9.28±0.70)%(P<0.05)。【结论】Losartan可减轻缺血/再灌注对大鼠胰腺病理改变、抑制细胞凋亡。

【Objective】To investigate the protective effect of losartan on acute ischemia reperfusion（I/R） injury in pancreas of rats.【Methods】Ninety Wister rats were randomly divided into 3 groups：（1）Control group：（2）Ischemia-reperfusion group;（3） losartan group.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 [（16.59±1.04）nmol/g and（26.96±1.51）nmol/g vs（20.10±0.69）nmol/g and（35.91±1.6）nmol/g,P〈0.05];and apoptosis [（5.44±0.93）% and（7.70±1.09）% vs（10.27±1.35）% and（18.59±1.02）%,P〈0.05].The administration of losartan increased expression of Bcl-2 [（12.48±0.90）% and（17.73±0.78）% vs（6.56±0.58）% and（9.28±0.70）%,P〈0.05].【Conclusion】Losartan can decrease the pathologic changes and suppress cell apoptosis in pancreas of rats with I/R.