临床肝胆病杂志2018，Vol.34Issue(2)：359-363,5.DOI:10.3969/j.issn.1001-5256.2018.02.028
绿原酸抑制JNK信号通路对非酒精性脂肪性肝病的防治作用
Chlorogenic acid exerts preventive and therapeutic effects on nonalcoholic fatty liver disease by inhibiting the JNK signaling pathway
摘要
Abstract
Objective To investigate the role of chlorogenic acid (CG) in nonalcoholic fatty liver disease (NAFLD) and possible molecular basis,since NAFLD is closely associated with insulin resistance and CG can regulate glucose and lipid metabolism and improve insulin resistance.Methods A total of 30 Sprague-Dawley rats were randomly divided into normal diet group (NG group),high-fat diet group (HG group),and chlorogenic acid group (CG group).All rats were given normal diet in week 1 as adaptive feeding;in weeks 2 and 3,the rats in NG group were given normal diet,and those in HG and CG groups were given high-fat diet;since week 4,the rats in NG and HG groups were given normal saline by gavage three times a week,and those in CG group were given CG by gavage three times a week.An automatic biochemical analyzer and radioimmunoassay were used to measure serum biochemical parameters,and a full-wavelength spectrophotometer was used to measure superoxide dismutase (SOD),malondialdehyde (MDA),and free fatty acid (FFA).A euglycemic-hyperinsulinemic clamp was used to measure insulin resistance.Western blot was used to measure autophagy-related proteins and c-Jun N-terminal kinase (JNK) proteins.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.A Pearson correlation analysis was used for correlation analysis.Results Compared with the NG group,the HG group had significantly higher body weight,liver index,liver wet weight,alanine aminotransferase (ALT),aspartate aminotransferase (AST),triglyceride (TG),total cholesterol (TC),tumor necrosis factor-α (TNF-α),and levels of MDA and FFA in liver homogenate and a significantly lower level of SOD (all P ＜0.05).Compared with the NG group,the HG group had significant increases in the levels of p-JNKi and JNK1 proteins and autophagy-related proteins LC3-Ⅰ,LC3-l,Beclin-1,Atg3,and Atg5 (all P ＜ 0.05).The protein expression of JNK1 was positively correlated with insulin resistance.Compared with the HG group,the CG group had significantly lower body weight,liver wet weight,liver index,levels of ALT,AST,TG,TC,and TNF-α,and levels of MDA and FFA in liver homogenate,a significantly higher level of SOD,and significantly lower expression of LC3-Ⅰ,LC3-Ⅱ,Beclin-1,Atg3,and Atg5 (all P ＜ 0.05).Conclusion CG improves liver injury and insulin resistance by inhibiting autophagy via the inactivation of the JNK pathway.CG may be a potential method for the treatment of NAFLD.关键词
非酒精性脂肪性肝病/绿原酸/JNK丝裂原活化蛋白激酶类/大鼠,Sprague-DawleyKey words
nonalcoholic fatty liver disease/chlorogenic acid/JNK mitogen-activated protein kinases/rats, Sprague-Dawley分类
医药卫生引用本文复制引用
延华,张颖,王欢,高艳琼,刘贵生,雷建园..绿原酸抑制JNK信号通路对非酒精性脂肪性肝病的防治作用[J].临床肝胆病杂志,2018,34(2):359-363,5.基金项目
陕西省自然科学基金(2016JM8142) （2016JM8142）
