白细胞介素1β转化酶抑制剂对胰腺炎大鼠胰腺细胞凋亡的诱导

Interleukin-1β-converting enzyme inhibitor induces apoptosis of pancreatic acinar cells during pancreatitis in rats

目的探讨白细胞介素(IL)1β转化酶(ICE)抑制剂诱导急性胰腺炎腺泡细胞凋亡的作用。方法120只SD大鼠随机分为假手术对照组(S)、胰腺炎组(P)和ICE抑制剂干预组(I),每组40只。各组造模后在2、6、12和24h4个时间点分别检测10只大鼠。I组于制模前48h开始腹腔注射ICE抑制剂0.25mg/100mg体质量,间隔12h注射一次。P组仅同时注射等量生理盐水。应用ELISA方法、细胞凋亡原位标记(TUNEL)染色等检测血清中淀粉酶、肿瘤坏死因子(TNF)-α、IL-1β和胰腺细胞凋亡。结果HE染色见胰腺组织中典型的细胞核固缩及凋亡小体形成。I组各个时间点病理学评分和血淀粉酶、TNF-α、IL-1β浓度均明显低于P组,胰腺细胞凋亡指数显著高于P组(P<0.01)。结论ICE抑制剂能减轻急性胰腺炎严重程度,其机制可能与其对炎症介质的抑制和诱导胰腺腺泡细胞的凋亡有关。

Objective To investigate the ability of interleukin-1β-converting enzyme （1CE） inhibitor to induce the apoptosis of pancreatic acinar ceils in rats with experimental acute pancreatitis. Methods One hundred and twenty SD rats were divided into three groups of sham operation（S）, acute pancreatitis（P） and ICE inhibitor intervention（I） with 40 rats each. Sodium deoxycholate was injected on the pancreatic membrane to establish acute pancreatitis model in group P and 1. The rats in group I were injected intraperitonealy ICE inhibitor 0. 25 mg/100 mg every 12 h beginning at 48 h before model establishment until the rats were killed and those in group P were given equal volume of normal saline. With ELISA and TUNEL methods, tumor necrosis factor （TNF）-α, interlcukin （IL） 1β and amylase were detected and the apoptosis of pancreatic acinar cells was observed at 2,6,12 and 24 h after induction of acute pancreatitis. Results Pathological results showed that there were pyknotie nuclei and apoptotic bodies in the acinar cells. TUNEL staining showed that the apoptotic index of pancreatic acinar cells in group I at 2,6, 12 and 24 h after the induction of acute pancreatitis was significantly higher and TNF-α,and interleukin（IL）-1β were lower than those in group P （P〈0.01）. Conclusion ICE inhibitor attenuates the severity of acute pancreatitis, which may be ralated to its effect of reducing systemic inflammatory cytokines and inducing apoptosis of pancreatic acinar cells.