AG490对重症急性胰腺炎大鼠胰腺腺泡细胞凋亡的影响

摘要

目的 探讨AG490对重症急性胰腺炎(SAP)大鼠胰腺腺泡细胞凋亡及凋亡基因FasL和Bcl-2表达的影响.方法 健康Wistar大鼠72只,按随机数字表法分为对照组(24只)、SAP模型组(24只)和AG490治疗组(24只).后2组采用5%牛磺胆酸钠胆胰管内逆行注入诱导SAP大鼠模型,3组大鼠均于术后6 h、12 h、24 h心脏采血,检测血清淀粉酶.剖腹取胰腺组织,光镜下观察胰腺组织病理改变并进行病理学评分,TUNEL法检测胰腺腺泡细胞凋亡指数,RT-PCR检测胰腺组织FasL、Bcl-2 mRNA的表达.结果 与对照组比较,SAP模型组大鼠胰腺病理损伤加重,病理评分增高,血清淀粉酶明显升高,胰腺腺泡细胞凋亡指数升高,FasL mRNA表达明显升高,Bcl-2 mRNA表达明显降低(P＜0.05或P＜0.01).与SAP模型组相比较,AG490治疗组大鼠胰腺病理损伤明显改善,病理评分降低,血清淀粉酶明显降低,胰腺腺泡细胞凋亡指数升高,FasL mRNA表达明显升高,Bcl-2 mRNA表达明显降低(P＜0.05或P＜0.01).结论 抑制JAK/STAT3信号通路可能通过调节凋亡相关基因,增加胰腺腺泡细胞凋亡,从而减轻胰腺炎症反应及病理损害.%Objective To investigate the effect of AG490 on the apoptosis of pancreatic acinar cells and expression of apoptosis gene FasL and Bcl-2 in rat model of severe acute pancreatitis (SAP). Methods Seventy-two healthy Wistar rats were randomly divided into control group (n=24), SAP group (n=24) and AG490 group (n=24). Heart blood samples were taken to detect serum amylase at 6 h, 12 h and 24 h after operation in three groups. Pancreatic tissue were observed under light microscope to analyze pathological changes and pathological scores. The index of pancreatic acinar cell apoptosis was detected by TUNEL. The expressions of FasL and Bcl-2 mRNA in pancreatic tissue was detected by RT-PCR. Results Compared with control group, the damage of pancreatic tissue was gradually increased, the serum level of amylase significantly increased (P＜0.01), the index of pancreatic acinar cell apoptosis increased, the expression of FasL mRNA was significantly increased, the expression of Bcl-2 mRNA was significantly decreased (P＜0.05 or P＜0.01) in SAP group. Compared with SAP group, the pancreatic injury was improved significantly, the serum amylase significantly decreased ( P＜0.01), the apoptosis index rate of pancreatic acinar cells was increased, the expression of FasL mRNA was significantly increased, and the expression of Bcl-2 mRNA was significantly decreased (P＜0.05 or P＜0.01) in AG490 group. Conclusion The inhibition of the JAK/STAT3 signaling pathway may regulate the apoptosis-related gene to increase the apoptosis of pancreatic acinar cells, thereby reducing the reaction and pathological damages of acute pancreatitis.