AG490对重症急性胰腺炎大鼠胰腺腺泡细胞凋亡的影响

Effects of AG490 on the apoptosis of pancreatic acinar cells in rat model of severe acute pancreatitis

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Fas L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Fas L、Bcl-2 m RNA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,Fas L m RNA表达明显升高,Bcl-2 m RNA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,Fas L m RNA表达明显升高,Bcl-2 m RNA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 detect- ed 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 in- creased, 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 apop- tosis 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.