南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (11): 1977-1983.doi: 10.12122/j.issn.1673-4254.2023.11.20

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基于HMGCR及PPARα信号通路探究雪莲果浸膏对高脂血症大鼠脂质代谢的影响

龚顺航，杨 杰，张金涛，吴兴林，江 山，张誉麟，龚广斌，吴 宁，孙见飞，吴遵秋   

  1. 贵州医科大学基础医学院化学与生物化学实验室，贵州 贵阳 550025
  • 出版日期:2023-11-20 发布日期:2023-12-08

Yacon root extract improves lipid metabolism in hyperlipidemic rats by inhibiting HMGCR expression and activating the PPARα/CYP7A1/CPT-1 pathway

GONG Shunhang, YANG Jie, ZHANG Jintao, WU Xinglin, JIANG Shan, ZHANG Yulin, GONG Guangbin, WU Ning, SUN Jianfei, WU Zunqiu   

  1. Laboratory of Chemistry and Biochemistry, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, China
  • Online:2023-11-20 Published:2023-12-08

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摘要： 目的 探究雪莲果（Yacon）浸膏对高脂血症（HLP）大鼠脂质代谢的影响和改善血脂异常的作用机制。方法 随机数表法取10只SD大鼠作为空白组（Normal），正常饮食；另取50只大鼠给予高脂饮食8周建立HLP模型，随机分为模型组（Mod）、非诺贝特阳性对照组（FEN，27 mg/kg），Yacon浸膏高、中、低剂量组（5、2.5、1.25 g/kg），10只/组。各组大鼠给予相应药物灌胃，Normal组、Mod组给予等体积生理盐水，干预8周。观察并记录大鼠体质量变化，采集肝脏、血清标本，计算肝脏系数；ELISA法检测血清中甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）水平；HE染色法观察肝组织病理变化；qPCR和 Western blot法分别检测3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）、过氧化物酶增殖物激活受体α（PPARα）、胆固醇7α-羟化酶（CYP7A1）、肉碱棕榈酰转移酶1（CPT-1）mRNA及蛋白表达水平。结果 FEN组和Yacon 5 g/kg组体质量增量、肝脏系数均低于Mod组（P<0.05）；FEN组和Yacon 5 g/kg组血清TG、TC、LDL-C水平均低于Mod组（P<0.05），HDL-C水平高于Mod组（P<0.05）；光镜下观察大鼠肝脏病理组织切片，Mod组可见脂肪样变性和空泡样改变等病理变化，药物各治疗组病理程度明显减轻且具有剂量依赖性；与Mod组相比，FEN组和Yacon 5 g/kg组大鼠肝组织中HMGCR mRNA及蛋白表达水平降低（P<0.001），PPARα、CYP7A1、CPT-1 mRNA及蛋白表达水平升高（P<0.001）。结论 Yacon浸膏可以降低HLP大鼠血清TG、TC水平，其机制可能与抑制肝脏HMGCR的表达和激活PPARα/CYP7A1/CPT-1信号通路，促进脂肪酸β氧化、胆汁酸代谢有关。

关键词: 雪莲果浸膏；高脂血症；脂质代谢；HMGCR；PPARα

Abstract: Objective To investigate the effect of yacon root extract on lipid metabolism in rats with hyperlipidemia (HLP) and its underlying mechanisms. Methods SD rat models of HLP induced by high- fat diet feeding for 8 weeks were randomized into the model group, fenofibrate treatment group (27 mg/kg), and yacon extract treatment groups at doses of 5, 2.5 and 1.25 g/kg (n=10). The rats were given corresponding drug treatments via gavage for 8 weeks. After the treatments, the rats were observed for body weight changes, liver coefficient, liver pathology, and serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The mRNA and protein expressions of HMGCR, PPARα, CYP7A1, and CPT-1 in the liver were detected using RT-qPCR and Western blotting. Results Compared with those in the model group, the rats treated with fenofibrate and 5 g/kg yacon root extract showed significantly slower body weight gain and lower liver coefficient (P<0.05) with lower serum levels of TG, TC, and LDL- C (P<0.05) but higher HDL-C level (P<0.05). The HLP rat models showed obvious fatty degeneration and vacuolar changes in the liver, which were significantly alleviated by fenofibrate treatment and by treatment with yacon root extract in a dose-dependent manner. Both fenofibrate and 5 g/kg yacon root extract significantly lowered the mRNA and protein expression levels of HMGCR (P<0.001) and increased the expressions of PPARα, CYP7A1, and CPT-1 in the liver of HLP rats (P<0.001). Conclusion Yacon root extract can reduce serum TG and TC levels in HLP rats possibly by inhibiting HMGCR expression and activating the PPARα/CYP7A1/CPT-1 signaling pathway, thereby promoting fatty acid β oxidation and bile acid metabolism.

Key words: yacon root extract; hyperlipidemia; lipid metabolism; HMGCR; PPARα