外源性胰岛素样生长因子-1对重症急性胰腺炎大鼠肠黏膜屏障损害的保护作用

Protective effect of exogenous insulin-like growth factor-1 on gut barrier function of severe acute pancreatitis:experiment with rats

目的研究外源性胰岛素样生长因子-1(IGF-1),对重症急性胰腺炎(SAP)大鼠肠黏膜屏障损害的保护作用及其机制。方法72只雄性Wistar大鼠按照随机数字表法分为假手术组(SO组),SAP组,IGF-1治疗组共三组,每组24只。每组再分为3个时相点(6h,12h,24h),每个时相点8只。通过胰胆管逆行注射5%牛磺胆酸钠制作大鼠SAP模型,假手术组用同样方法经胰胆管逆行注射生理盐水,IGF-1组分别于术前30min和术后3h经后肢内侧皮下注射IGF-1。各组动物分别于术后6h、12h、24h处死8只,检测各组大鼠血浆淀粉酶、内毒素及二胺氧化酶(DAO),观察小肠组织病理学变化并进行评分,TUNEL法检测小肠黏膜上皮细胞凋亡。结果IGF-1治疗组大鼠血浆淀粉酶、内毒素及二胺氧化酶水平均显著低于SAP组;小肠黏膜上皮细胞凋亡指数及组织学病理评分亦显著低于SAP组。结论外源性IGF-1可以减轻SAP时肠黏膜的损伤及内毒素血症,对肠黏膜屏障具有一定的保护作用,其机制可能与IGF-1可以抑制SAP时肠黏膜上皮细胞的过度凋亡有关。

Objective To investigate the protective effect of exogenous insulin-like growth factor-1 （IGF-1） on the gut barrier function dysfunction induced by severe acute pancreatitis （SAP） and its possible mechanism. Methods 72 male Wistar rats were randomly divided into 3 equal groups： SAP group （SAP） undergoing retrograde infusion of 5.0 % sodium taurocholate so as to establish SAP models, IGF-1 treatment group, undergoing subcutaneous injection of IGF-1 30 rain before and 3 h after the operation, and sham operation （SO） group, undergoing retrograde infusion of normal saline. 6, 12, and 24 hours later 8 rats in each group were killed with the blood samples taken from the right ventricles to detect the serum amylase, endotoxin, and diamine oxydase （DAO）. Specimens of small intestine were obtained to undergo pathological examination. TUNEL method was used to observe the apoptosis of mucosal cells. Resu Its The serum amylase levels of the SAP group at different time points were all significantly higher than those of the SO group （all P 〈0.05）.,and the IGF-1 group was not significantly different from that of the SAP group （P 〉0.05） 6 h after operation, but significantly lower than that of the SAP group 12 h and 24 h after the operation （both P 〈0.05）; however, the serum amylase levels of the IGF-1 group at different time points were not significantly different from those of the SO group （all P 〉0.05）. Theserumendotoxinlevels 12 h and 24 h after operation of the SAP group were both significantly higherthanthose of the SO group （both P 〈0.01）, and 12 h after operation of the IGF-1 group was significantly lower than that of the SAP group（P 〈0.01）. The pathological scores of the small intestine at different time points of the SAP group were all significantly higher than those of the SO group （all P 〈0.05）, and the IGF-1 group were all significantly lower than those of the SAP group （all P 〈0.05）. The apoptotic indexes at different time points of the SAP group were all significantly higher than those of the SO group （all P 〈0.01）,and the IGF-1 group were all significantly lower than those of the SAP group （all P 〈0.01）, but not significantly different from those of the SO group （all P 〉0.05）. Conclusion Exogenous IGF-1 alleviates SAP- induced injury to intestinal mueosal and endotoxemia.The mechanism may be that IGF-1 inhabits excessive apoptosis of the intestinal mucosal.