基于HIF-1α/PPARγ研究荷叶颗粒对非酒精性脂肪肝大鼠脂代谢及SREBP-1c表达的影响

Effects of Heye granule on lipid metabolism and SREBP-1c expression in nonalcoholic fatty liver rats based on HIF-1α/PPARγ

目的基于缺氧诱导因子-1α(HIF-1α)/过氧化物酶体增殖物激活受体γ(PPAR-γ)研究荷叶颗粒对非酒精性脂肪肝大鼠脂代谢及胆固醇调节元件结合蛋白-1c(SREBP-1c)表达的影响。方法将SD大鼠分为对照组、模型组、荷叶颗粒低剂量组(0.5g/kg)、荷叶颗粒中剂量组(1.0g/kg)、荷叶颗粒高剂量组(1.5g/kg)、多烯磷脂酰胆碱组(14.25mg/kg),每组12只,对照组以普通饲料喂养,其余各组以高脂饲料喂养8周建立非酒精性脂肪肝大鼠模型,分组处理后,检测肝指数,丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)水平,三酰甘油(TG)及游离脂肪酸(FFA)水平;以HE检测各组大鼠肝组织病理变化;以酶联免疫吸附(ELISA)试剂盒检测各组大鼠血清肿瘤坏死因子α(TNF-α)及白细胞介素6(IL-6)水平,以Western blot检测肝组织中HIF-1α、PPARγ、SREBP-1c蛋白表达。结果与对照组相比,模型组大鼠肝组织呈现脂肪变性,并有大量脂肪空泡,肝索排列紊乱,肝细胞坏死等病理损伤,肝指数、ALT、AST、TG、FFA、TNF-α及IL-6水平,HIF-1α、PPARγ及SREBP-1c蛋白表达明显升高(P<0.05)。与模型组相比,荷叶颗粒低、中、高剂量组、多烯磷脂酰胆碱组大鼠肝组织病理损伤减轻,肝指数、ALT、AST、TG、FFA、TNF-α及IL-6水平,HIF-1α、PPARγ及SREBP-1c蛋白表达降低(P<0.05),荷叶颗粒各剂量组呈剂量依赖性,荷叶颗粒高剂量组与多烯磷脂酰胆碱组相比,差异无统计学意义(P>0.05)。结论荷叶颗粒剂可下调SREBP-1c表达,降低非酒精性脂肪肝大鼠血脂水平,减轻肝组织炎症及脂肪变性,改善其肝功能,可能是通过抑制HIF-1α/PPARγ信号通路实现的。

Objective To study the effects of Heye granule on lipid metabolism and SREBP-1 cexpression in rats with nonalcoholic fatty liver based on HIF-1α/PPARγ.Methods SD rats were randomly divided into the control group,the model group,the Heye granule low dose group(0.5 g/kg),the medium dose group(1 g/kg),the high dose group(1.5 g/kg)and the Essentiale group(14.25 mg/kg),with 12 rats in each group.The control group was fed with ordinary feed,and the other groups were fed with high-fat diet for 8 weeks to establish nonalcoholic fatty liver model.After treatment,the liver index,alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels,triacylglycerol(TG)and free fatty acids(FFA)were measured.Hematoxylin eosin staining(HE)was used to detect the pathological changes of liver tissue.The levels of TNF-αand IL-6 were detected by ELISA,and the expressions of HIF-1α,PPARγand SREBP-1 cin liver tissue were detected by Western blot.Results Compared with the control group,the liver tissue of the model group showed fatty degeneration,with a large number of fat vacuoles,disorder of liver cord arrangement,necrosis of liver cells and other pathological damages,and liver indexes,ALT,AST,TG,FFA,TNF-αand IL-6 levels,HIF-1α,PPARγand SREBP-1 cprotein expressions increased significantly(P<0.05).Compared with the model group,the pathological damage of the liver tissue in the Heye granule low,middle and high dose groups and the Essentiale group was reduced,liver indexes,ALT,AST,TG,FFA,TNF-αand IL-6 levels,HIF-1α,PPARγand SREBP-1 cprotein expressions decreased(P<0.05).The Heye granule groups were dose-dependent,and there was no significant difference between the Heye granule high dose group and the Essentiale group(P>0.05).Conclusion Heye granule can down-regulate the expression of SREBP-1 c,decrease the level of blood lipid,reduce the inflammation and steatosis of liver tissue,and improve the liver function of nonalcoholic fatty liver rats,which may be achieved by suppressing HIF-1α/PPARγsignaling pathway.