[关键词]
[摘要]
目的 研究三七粉对高脂血症模型大鼠的调血脂作用及其作用机制。方法 采用高脂饲料配合高脂乳剂诱导高脂血症大鼠模型,高脂血症大鼠分别ig给予高、中、低剂量(1.08、0.54、0.27 g/kg)三七粉,以脂必妥(37.8 mg/kg)和辛伐他汀(1.8 mg/kg)为阳性对照,各组每天给药1次,连续给药8周。给药结束后测定各组大鼠血清中总胆固醇(TC)、三酰甘油(TG)和低密度脂蛋白-胆固醇(LDL-C)水平,同时检测血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活性;对肝组织进行石蜡切片和HE染色,观察组织病理变化;采用RT-PCR法检测肝组织中低密度脂蛋白受体(LDLR)、组蛋白/非组蛋白去乙酰化酶(沉默调节因子1,SIRT1)和肝X受体α亚型(LXR-α)的基因表达,同时采用Western blotting法检测肝组织中胆固醇调节元件结合蛋白-2(SREBP-2)及SREBP裂解激活蛋白(SCAP)的表达水平。结果 三七粉显著降低高脂血症大鼠血清中TC、TG和LDL-C水平及AST、ALT活性;组织学观察结果显示三七粉明显减轻了肝损伤和脂肪肝;分子水平结果显示,三七粉能上调LDLR和SIRT1、下调LXR-α基因表达。同时,三七粉显著降低了SREBP-2和SCAP的蛋白表达。结论 三七粉具有调血脂、保护肝脏的作用,这可能与三七粉上调SIRT1、下调LXR-α基因表达,进而下调SCAP/SREBP-2信号通路抑制胆固醇合成,以及上调LDLR的基因表达提高肝脏对血液循环中LDL-C的摄取的机制有关。
[Key word]
[Abstract]
Objective To investigate the hypolipidemic effects of powder of Panax notoginseng (PPN) and explore its possible mechanism. Methods Hyperlipidemic rats model was established, and orally given three dosages of PPN for 8 weeks. The levels of serum ALT, AST, TC, TG, and LDL-C were detected. The pathological changes of liver tissues were observed by H&E staining. Gene expressions of hepatic low density lipoprotein receptor (LDLR), SIRT1, and LXR-α were measured with RT-PCR analysis. Protein expression of SREBP-2 and SCAP was determined by Western blotting. Results Three dosages of PPN significantly decreased serum ALT, AST, TC, TG, and LDL-C levels. Histological data indicated that PPN notably reduced liver injury and hepatic steatosis in hyperlipidemic rats. In molecular study, mRNA expression of hepatic LDLR and SIRT1 was up-regulated and LXR-α gene expression was down-regulated in PPN treated rats. Additionally, PPN significantly reduced protein expression of SREBP-2 and SCAP. Conclusion The positive effect of PPN on hyperlipidemic rats may be related to the inhibition of cholesterol synthesis of PPN through the up-regulation of SIRT1 and down-regulation of LXR-α and SCAP/SREBP-2 signaling pathway. Additionally, PPN could up-regulate hepatic LDLR mRNA expression and improve uptake of LDL-C in circulation.
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[基金项目]
国家中医药管理局2015年中医药部门公共卫生专项资金(中药科技类)项目“中药炮制技术传承基地”(湖北中医药大学基地)