白藜芦醇对重症急性胰腺炎大鼠胰腺细胞凋亡的影响

Effect of Resveratrol on Apoptosis of Pancreatic Cells in Rats with Severe Acute Pancreatitis

目的:探讨白藜芦醇对大鼠重症急性胰腺炎(SAP)胰腺腺泡细胞凋亡及凋亡调控基因Bax和Bcl-2表达的影响。方法:L-精氨酸盐酸盐分次间隔2 h注入大鼠腹腔和皮下以建立SAP模型,48只大鼠随机分为白藜芦醇(RES)治疗组、非治疗(SAP)组(各20只)和正常对照(NS)组(8只)。RES组于皮下注射L-精氨酸盐酸盐后立即腹腔注射白藜芦醇。各组在末次注射后分别于6、12、24和48 h测血清淀粉酶、胰腺湿/干重比值,观察各组胰腺组织的病理变化并评分,免疫组化SP法检测胰腺组织Bax和Bcl-2基因表达,同时行末端脱氧核苷酸转换酶介导的原位末端标记检测胰腺细胞凋亡情况。结果:RES组12、24 h血清淀粉酶活性明显下降,24、48 h胰腺湿/干重比值降低,胰腺组织出血坏死减轻,24、48 h病理评分均低于SAP组(P<0.05);给药后6、12 h细胞凋亡指数和Bax、Bcl-2基因表达均高于SAP组(P<0.01)。结论:白藜芦醇可诱导SAP受损胰腺细胞凋亡,抑制血清淀粉酶释放,减轻大鼠胰腺病理损伤,其机制可能是通过上调Bax和Bcl-2基因的表达。

Objective： To investigate the effects of resveratrol on apoptosis of pancreatic cells and apoptesis-regulated gene Bax and Bcl-2 in rats with severe acute pancreatitis（SAP）. Methods： L-arginine was given to rats by intraperitoneal and subcutaneous injection twice at an interval of 2 hours to establish the model of SAP. Forty-eight rats were ran- domly divided into resveratrol-treated （ RES, n = 20） group, SAP model （ SAP, n = 20） group and control （ NS, n = 8） group. Resveratrol was given to the rats of RES group by intraperitoneal injection after the subcutaneous injection of L- arginine. Rats were sacrificed at 6, 12, 24 and 48 hours after the last injection to determine the levels of ,serum amylase and the wet/dry weight ratio of pancreas. Pancreatic histopathological score based on microscopic changes was evaluated. Apoptosis of pancreatic cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotion nick end label- ing method, and the expression of Bax and Bcl-2 gene was detected by SP immunohistochemical technique. Results： After resveratrol being rejected, the ,serum amylase decreased significantly at 12 and 24 hours, the wet/dry ratio of pancreas reduced at 24 and 48 hours. The pathological changes of pancreas alleviated obviously. The apoptopic index of pancreatic cells increased significantly compared with the SAP group at 6 and 12 hours, corresponding with the expression of the Bax and Bcl-2 gene. Conclusion： Resveratrol can significantly alleviate the pancreatic pathological dana,aged conditions of SAP in rats via the induction of apoptosis in injured pancreatic cells. Up-regulation of Bax and Bcl-2 gene expression might be the mechanism of resveratrol in treating SAP in rats.