白细胞介素1受体拮抗剂诱导急性胰腺炎大鼠胰腺腺泡细胞凋亡机制的研究

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)干预急性胰腺炎的可能机制。方法:72只SD大鼠,随机分为胰腺炎组、IL-1Ra干预组、对照组,每组24只,各组造模后在1,2,6和12 h 4个时间点分别检测6只大鼠。干预组分别于制模前12,6,2 h及制模时各注射IL-1Ra 1 mg/100 mg体质量,胰腺炎组仅同时注射等量生理盐水。应用细胞凋亡原位标记(TUNEL)染色、免疫组化技术等检测胰腺细胞凋亡及凋亡调控基因Bax,Bcl-2,Fas,FasL的蛋白表达。结果:干预组1,2,6和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Bax、Fas的表达,干预组各时间点胰腺细胞Bax、Fas染色阳性率明显高于胰腺炎组(均P<0.01);对照组未见Bcl-2表达,干预组各时间点胰腺细胞Bcl-2染色阳性率与胰腺炎组相比无显著差异性(均P>0.05);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干预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Bax和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。

Mchanism by which IL-1Ra induces apoptosis of pancreatic acinar cells during pancreatitis in rats

Objective:To investigate the ability of interleukin-1 receptor antagonist to induces apoptosis of pancreatic acinar cells during experimental acute pancreatitis in rats.Methods:A toatal 72 rats were randomly divided into three groups(each with 24 rats) :pancreatitis group,IL-1Ra interference group and control group.Under the pancreatic membrane injection of sodium deoxycholate was carried out to establish acute pancreatitis model in SD rats.Six rats were sacrificed at 1,2,6 and 12 h after the model was made.The apoptosis of pancreatic acinar cells was observed and apoptotic index was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling(TUNEL) method.The expression of apoptosis regulated gene Fas,FasL,Bax,Bcl-2 was detected by immunohistochemical 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 and Bax staining cells and no Bcl-2 positive staining cells in normal pancreatic tissues.The positive rate of Bax protein in IL-1Ra treated group at 1,2,6 and 12 hours was significantly higher than those of ANP group respectively(all P<0.01).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),while Bcl-2 remained unchanged in pancreatic acinar cells during acute pancreatitis,and the expression of FasL could only be detected in infiltrative inflammatory cells. Conclusion: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 may be associated with activity regulation of Bax,Fas/ FasL system.