连续性血液透析滤过联合依那普利对急性重症胰腺炎大鼠肾功能及肠功能的改善作用

Continuous hemodiafiltration combined with enalapril improves renal and intestinal function in rats with severe acute pancreatitis

目的探究连续性血液透析滤过联合依那普利对急性重症胰腺炎大鼠肾功能及肠功能的改善作用。方法60只SD大鼠随机分为5组:对照组、模型组、连续性血液透析滤过组、依那普利组及连续性血液透析滤过联合依那普利组,除对照组外均采用牛黄胆酸钠诱导急性重症胰腺炎大鼠模型,连续性血液透析滤过组造模后给予连续性血液透析滤过12 h;依那普利组术前7 d灌胃10 mg/(kg·d)的依那普利,每天1次;连续性血液透析滤过联合依那普利组作相应的联合处理。采用HE染色观察大鼠胰腺、肾及肠粘膜组织病理变化,检测血浆内毒素(ET)、D-乳酸(D-LC)、血清淀粉酶(AMY)、尿素氮(BUN)和肌酐(Cr)水平,FITC-Dextran通透实验检测肠道通透性,Western Blot检测大鼠α-血管平滑肌肌动蛋白(α-SMA)、E钙黏素(E-cadherin)、高迁移率族蛋白B1(HMGB1)及闭合蛋白(occludin)的表达。结果与模型组相比,连续性血液透析滤过联合依那普利可有效减轻急性重症胰腺炎大鼠胰腺、肾及肠粘膜组织损伤,显著降低大鼠肠粘膜通透性、血清AMY、BUN、Cr、血浆ET、D-LC水平、组织α-SMA及HMGB1的表达,显著提高E-cadherin和Occludin的表达,且作用效果优于单项处理。结论连续性血液透析滤过联合依那普利可明显改善急性重症胰腺炎所致的肾及肠组织损伤,有助于肾功能及肠功能的恢复。

Objective To explore the beneficial effects of continuous hemodiafiltration(CHDF)combined with enalapril on renal and intestinal function in rats with severe acute pancreatitis(SAP).Methods Sixty Sprague-Dawley rats were randomly divided into a control group and four treatment groups:SAP model,CHDF,enalapril,and CHDF+enalapril.Rats in the treatment groups were induced with SAP using sodium taurocholate.After modeling,the CHDF group was given CHDF for 12 h,and the enalapril group was given enalapril 10 mg/kg/d by gavage,for 1 day.The CHDF+enalapril group was given both treatments simultaneously.Histopathological changes in the pancreas,kidney and intestinal mucosa were observed by hematoxylin and eosin staining.The plasma levels of endotoxin(ET)and D-lactic acid(D-LC),and serum levels of amylase(AMY),blood urea nitrogen(BUN)and creatinine(Cr)were measured.A fluorescein isothiocyanate-dextran permeability test was used to examine intestinal permeability.Western blotting was used to detect expression ofα-vascular smooth muscle actin(α-SMA),E-cadherin,high mobility groupbox protein 1(HMGB1)and occludin.Results Compared with the model,CHDF+enalapril had the following effects in rats with SAP:effectively alleviated damage to the pancreas,kidney and intestinal mucosal tissues;significantly reduced intestinal mucosal permeability,the levels of serum AMY,BUN and Cr and plasma ET and D-LC,and expression ofα-SMA and HMGB1 in tissues;and significantly increased expression of E-cadherin and occludin.The combined action effect was better than that of either single treatment.Conclusions CHDF combined with enalapril significantly improved renal and intestinal tissue damage caused by SAP,which contributed to the recovery of renal and intestinal function.