摘要
目的探讨双歧杆菌(Bifidobacterium,BIFI)对慢性酒精性肝损伤(chronic alcoholic liver injury,CALI)大鼠肝功能的保护或影响作用,并初步探讨其机制。方法将SD大鼠随机分为CALI组,美他多辛(90 mg/kg)组,BIFI低(500 mg/kg)、中(1000 mg/kg)、高(2000 mg/kg)剂量组,沉默信息调节蛋白1(silent information regulatory protein 1,SIRT1)抑制剂Tenovin-6(25 mg/kg)组。CALI组及空白对照组给予等体积生理盐水灌胃。8周后,分析各组大鼠肝功能;检测肝组织和血清中TG、TC水平;苏木素-伊红(HE)染色观察肝组织病理变化;蛋白印迹(WB)法分析肝组织中SIRT1、chREBP表达情况。结果与对照组比较,CALI组大鼠肝功能明显下降,血液中ALT、AST水平明显升高(P<0.05),肝组织呈脂肪性病理损伤,肝组织和血清中TG、TC水平明显升高(P<0.05),SIRT1蛋白表达明显降低(P<0.05),chREBP蛋白表达明显增高(P<0.05);与CALI组比较,BIFI低、中、高剂量组大鼠CALI组大鼠肝功能明显增强,血液中ALT、AST水平明显降低(P<0.05),肝组织病理损伤明显减轻,肝组织和血清中TG、TC水平明显降低(P<0.05),SIRT1蛋白表达明显升高(P<0.05),chREBP蛋白表达明显降低(P<0.05)。以上效应均可被SIRT1特异性抑制剂Tenovin-6逆转。结论 BIFI可能通过调控SIRT1/ChREBP表达抑制脂质堆积,实现对慢性酒精性肝损伤大鼠的保护。
Objective To investigate the protective effect of Bifidobacterium(BIFI)on liver function in rats with chronic alcoholic liver injury(CALI)and to explore the mechanism involved.Methods SD rats were randomly divided into a CALI group,metadoxine(90mg/kg)group,BIFI low-(500mg/kg),medium-(1000mg/kg),and high-dose(2000mg/kg)groups,and SIRT1inhibitor Tenovin-6(25mg/kg)group.The CALI group and a blank control group were given equal volumes of normal saline.After8weeks,liver function of each group was analyzed.Levels of TG and TC in liver tissue and serum were determined.The pathological changes of liver tissue were observed by hematoxylin-eosin staining.The expression of SIRT1and chREBP in liver tissue was analyzed by western blotting.Results Compared with the control group,the liver function of the rats in the CALI group decreased significantly,and the levels of ALT and AST in the blood increased significantly(P<0.05).In addition,liver tissue underwent fatty pathological damage.The levels ofTG and TC in liver tissue and serum were significantly increased(P<0.05),the expression of SIRT1protein wassignificantly decreased(P<0.05),and the expression of chREBP protein was significantly increased(P<0.05).Compared with the CALI group,the liver function of the rats in the low-,middle-,and high-dose BIFI groups wassignificantly enhanced.The levels of ALT and AST in the blood were also significantly decreased(P<0.05),thepathological damage of liver tissue was significantly reduced,and the levels of TG and TC in liver tissue and serum weresignificantly decreased(P<0.05),the expression of SIRT1protein was significantly increased(P<0.05),and theexpression of chREBP protein was significantly decreased(P<0.05).All of the above effects could be reversed by theSIRT1-specific inhibitor Tenovin-6.Conclusions BIFI may inhibit the accumulation of lipids by regulating SIRT1/ChREBP expression and protect rats from chronic alcoholic liver injury.
作者
林惠武
林燕琼
林志辉
LIN Huiwu;LIN Yanqiong;LIN Zhihui(Department of Pharmacy, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China;Department of Gastroenterology, Fujian Provincial Hospital, Fuzhou 350001)
出处
《中国实验动物学报》
CAS
CSCD
北大核心
2018年第6期760-765,共6页
Acta Laboratorium Animalis Scientia Sinica
基金
福建省2015年医药卫生人才科研计划(2015-CX-1)~~
