白细胞介素-1受体拮抗剂在急性胰腺炎中作用及机制探讨

目的 从胰腺腺泡细胞凋亡的角度探讨白细胞介素-1受体拮抗剂（IL-1Ra）在急性胰腺炎中的作用及机制。方法 用牛磺胆酸钠建立大鼠急性坏死性胰腺炎模型，IL-1Ra腹腔注射诱导胰腺腺泡细胞凋亡，并应用细胞凋亡原位标记检测(TUNEL) 染色、免疫组化等技术检测胰腺细胞凋亡及Fas/FasL的蛋白表达。结果 干预组1、2、6、12 h胰腺细胞凋亡指数显著高于胰腺炎组相应时间点(均P <0.01)；对照组见较弱的Fas的表达，干预组各时间点胰腺细胞Fas染色阳性率明显高于胰腺炎组(均P < 0.01) ；胰腺炎组、干预组中均没有见到胰腺腺泡细胞中FasL 表达，但是在间质中均可见浸润的炎性细胞FasL免疫组化染色阳性。结论 IL-1Ra减轻急性胰腺炎的机制可能不仅限于对炎症反应的抑制，它可能是通过上调凋亡调控基因Fas/ FasL系统的表达，诱导胰腺腺泡细胞的凋亡从而减轻胰腺炎的严重程度。

The effect and mechanism by which IL-1Ra induces apoptosis of pancreatic acinar cells during pancreatitis in rats

Objective To investigate the mechanism of interleukin-1 receptor antagonist to induces apoptosis of pancreatic acinar cells during experimental acute pancreatitis in rats. Methods Under the pancreatic membrane injection of sodium deoxycholate was carried out to establish acute pancreatitis model in SD rats. Interleukin-1 receptor antagonist (IL-1Ra) was injected intraperitonealy. The apoptosis of pancreatic acinar cells was observed and apoptotic index was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method, and the expression of apoptosis associated protein Fas , FasL were detected by immunohistochemistry technique. Results Results from the TUNEL staining showed that the apoptotic index of pancreatic acinar cells in treated group at 1、2、6 and 12 hours after the induction of acute pancreatitis was significantly higher than ANP and control group at the same time(all P < 0.01).Immunohistochemical analysis showed that there were weak Fas staining cells in normal pancreatic tissues. The positive rate of Fas protein in IL-1Ra treat group at 1、2、6 and 12 hour was markedly higher than that of ANP group (all P < 0.01) , and the expression of FasL could only be detected in infiltrative inflammatory cells.Conclusions During acute pancreatitis , induction of apoptosis in injured pancreatic acinar cells to reduce inflammatory response might be one of the mechanisms of IL-1Ra in treating acute pancreatitis in mice.The acinar cell apoptosis induced by IL-1Ra is associated with activity regulation of Fas/ FasL system.