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  

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

作　　者：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 GONG Shunhang;YANG Jie;ZHANG Jintao;WU Xinglin;JIANG Shan;ZHANG Yulin;GONG Guangbin;WU Ning;SUN Jianfei;WU Zunqiu(Laboratory of Chemistry and Biochemistry,School of Basic Medical Sciences,Guizhou Medical University,Guiyang 550025,China)

机构地区：[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　　处：《南方医科大学学报》2023年第11期1977-1983,共7页Journal of Southern Medical University

基　　金：国家自然科学基金(8206776);贵州省科技计划项目[黔科合LH字(2020)1Y388];2021年贵州省大学生创新创业训练计划项目[202110660031];2022年度乡村经济振兴研究与农业产业技术攻关项目专项研究课题[26222190612];2023年贵州省大学生创新创业训练计划项目[S202310660098]。

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。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 acidβoxidation and bile acid metabolism.

关 键 词：雪莲果浸膏 高脂血症 脂质代谢 HMGCR PPARΑ 

分 类 号：R285.5[医药卫生—中药学]