姜黄素抑制肝脏17β-羟类固醇脱氢酶2改善非酒精性脂肪性肝病

摘要

目的 探讨肝脏17β-羟类固醇脱氢酶2(17β-HSD2)在姜黄素改善非酒精性脂肪性肝病(NAFLD)中的作用.方法 将24只SD大鼠随机分为普食组(8只)、高脂组(8只)、姜黄素组(8只),对3组大鼠行肝脏组织病理、血清ALT、AST及肝脏脂质检测、蛋白组学及相关检测并进行比较.结果 与普食组比较,高脂组大鼠肝脏脂滴明显增多,血清ALT、AST及肝脏甘油三酯水平明显升高(P<0.01),肝脏17β-HSD2基因及蛋白表达水平明显升高(P<0.05),血清雌二醇及其肝脏下游基因过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)及过氧化物酶体增殖物激活受体α(PPARα)表达水平明显降低(P<0.05).而与高脂组比较,姜黄素组肝脏17β-HSD2表达水平明显下降(P<0.05),血清雌二醇及肝脏中PGC 1α、PPARα表达水平均明显升高(P<0.05).结论 姜黄素可能通过抑制肝脏17β-HSD2表达,减少雌激素灭活,上调肝脏PGC-1α及脂肪酸β氧化相关基因表达,改善NAFLD.%Objective To investigate the effect of curcumin on 17β-hydroxysteroid dehydrogenase 2 (17β-HSD2)in non-alcoholic fatty liver disease(NAFLD)in rats.Methods Twenty-four SD rats were randomly divided into normal diet(ND)group,high-fat diet(HFD)group and HFD+curcumin(HFD+C) group with eight rats in each group.Pathology,lipid and proteomics analysis of hepatic tissue,serum ALT and AST in rats of the three groups were detected and compared.Results Lipid drops and triglyceride in liver,serum ALT and AST increased significantly in HFD group compared to ND group(P<0.01).Also, rats in HFD group had a higher expression of hepatic 17β-HSD 2 gene and protein than those in ND group (P<0.05).Compared to ND group,the levels of serum estrogen and mRNA of its down-stream genes in liver,including PGC-1α and PPARα decreased in HFD group(P <0. 05). While the expression of 17β-HSD2 in liver tissues decreased and expression of serum estrogen and PGC-1α,PPARα in liver tissues increased compared with HFD group(P<0.05).Conclusion Curcumin might alleviate NAFLD through increasing expression of PGC-1α and hepatic fatty acid β-oxidation related genes levels by inhibiting expression of 17β-HSD2 and reducing inactivation of estrogen.