从CRTC2/SREBP1调节探讨三七总皂苷改善非酒精性脂肪肝大鼠脂质代谢的作用

Effects of Panax notoginseng spaponins on the lipid metabolism of nonalcoholic fatty liver disease rat via regulating expression of CRTC2 and SREBP1

目的:研究三七总皂苷对固醇调节元件结合转录因子1(SREBP1)、CREB转录激活因子2(CRTC2)的调节与改善早期非酒精性脂肪肝(NAFLD)大鼠脂质代谢的作用。方法:108只雄性SD大鼠随机分为正常组,模型组,非诺贝特组(18mg/kg),三七总皂苷低、中、高剂量组(9、18、36mg/kg),灌胃给药(10 mL·kg^(-1)·d^(-1)),检测第8、12周各组大鼠外周血肝功能指标;HE染色观察肝组织病理学形态;免疫组化法和Western Blot法检测SREBP1、CRTC2蛋白在肝脏细胞中的表达情况;RT-PCR检测SREBP1、CRTC2 mRNA表达情况。结果:与模型组比较,非诺贝特组及三七总皂苷高、中剂量组可有效控制NAFLD大鼠体质量增长;非诺贝特组肝指数高于模型组和正常组(P<0.05);与模型组比较,各给药组大鼠血清肝功能指标均显著下降(P<0.01,P<0.05),且三七总皂苷对NAFLD大鼠肝脏脂质沉积具有一定改善作用;三七总皂苷高剂量组显著下调肝组织中SREBP1、CRTC2蛋白及mRNA相对表达量(P<0.01,P<0.05)。结论:三七总皂苷可通过抑制SREBP1、CRTC2表达有效降低NAFLD大鼠转氨酶水平及血脂指标,从而调节脂质代谢。

Objective: To study the effects of Panax notoginseng spaponins(PNS) on lipid metabolism of nonalcoholic fatty liver(NAFLD) and its effects on the expression of sterol regulatory element binding transcription factor 1(SREBP1)and CREB regulated transcription coactivator 2(CRTC2). Methods: A total of 108 male SD rats were randomly divided into six groups: normal group, model group, Fenofibrate group(18 mg/kg), and PNS low, medium and high dose groups(9, 18, 36 mg/kg). Normal group and model group were administrated with normal saline for 10 mL·kg^(-1)·d^(-1), respectively. The indexes of liver function in peripheral blood of rats in each group were measured at the 8th and 12th weeks. Pathological changes were observed by HE staining. The expression of SREBP1 and CRTC2 were determined by immunohistochemical staining and Western Blot. The mRNA expression of SREBP1 and CRTC2 were detected by real-time PCR. Results: Compared with the model group, Fenofibrate group and the PNS high and medium dose group can effectively control the weight growth of NAFLD rats. The liver index of Fenofibrate group was higher than control group and model group(P<0.05). Compared with the model group, the serum liver function indexes of rats in the treatment groups decreased significantly(P<0.01, P<0.05). PNS showed some ameliorative effects on hepatic lipid deposition in NAFLD rats. The PNS high dose group can significantly down regulate the relative expression of SREBP1, CRTC2 protein and mRNA in liver tissue(P<0.01, P<0.05). Conclusion: PNS can effectively reduce aminotransferase levels and lipid indicators in NAFLD rats by inhibiting SREBP1 and CRTC2 expression, thus regulating lipid metabolism.