摘要
目的 观察瓜蒌薤白对高脂血症小鼠肝脏三酰甘油(triglyceride, TG)合成及沉默信息调节因子1(silent information regulator 1,SIRT1)/腺苷酸活化蛋白激酶(AMP-activated protein kinase, AMPK)通路的影响。方法 将40只高脂饲料喂养20周的载脂蛋白E基因敲除小鼠随机分为模型组,瓜蒌薤白低、中、高剂量组,阿托伐他汀组,每组8只;另设8只具有相同遗传背景的C57BL/6J小鼠作为空白组。酶法检测血清TG、总胆固醇(total cholesterol, TC)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol, LDL-C)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C)水平;ELISA及qRT-PCR法检测肝脏脂肪酸合成酶(fatty acid synthase, FAS)和乙酰辅酶A羧化酶(acetyl CoA carboxylase, ACC)含量及mRNA表达水平;Western blot及qRT-PCR法检测肝脏胆固醇调节元件结合蛋白1(sterol regulatory element-binding protein-1,SREBP-1)、碳水化合物反应元件结合蛋白(carbohydrate response element-binding protein, ChREBP)、SIRT1、AMPK蛋白及mRNA表达水平。结果 瓜蒌薤白降低血清TG、TC及LDL-C水平,升高血清HDL-C水平,降低肝脏TG合成酶FAS和ACC含量及mRNA表达水平,下调肝脏TG合成蛋白SREBP-1、ChREBP表达水平,显著上调SIRT1表达水平,下调AMPK表达水平。结论 瓜蒌薤白调节高脂血症小鼠血脂水平的机制可能与其激活SIRT1/AMPK通路,抑制肝脏TG合成相关蛋白及合成酶表达,抑制TG内源性合成有关。
Objective To investigate the effect of Fructus Trichosanthis-macrostem onion on hepatic triglyceride(TG)synthesis and the SIRT1/AMPK pathway in hyperlipidemia mice.Methods A total of 40 mice with apolipoprotein E gene knockout were given high-fat feed for 20 weeks and were then randomly divided into model group,atorvastatin group,and low-,middle-,and high-dose Fructus Trichosanthis-macrostem onion groups,and 8 C57BL/6J mice with the same genetic background were enrolled as blank group.The enzymatic method was used to measure the serum levels of total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C);ELISA and qRT-PCR were used to measure the content and mRNA expression levels of fatty acid synthase(FAS)and acetyl-CoA carboxylase(ACC)in mouse liver;Western blot and qRT-PCR were used to measure the protein and mRNA expression levels of sterol regulatory element-binding protein-1(SREBP-1),carbohydrate response element-binding protein(ChREBP),silent information regulator 1(SIRT1),and AMP-activated protein kinase(AMPK)in mouse liver.Results Fructus Trichosanthis-macrostem onion reduced the serum levels of TG, TC, and LDL-C and increased the serum level of HDL-C. It also reduced the content and mRNA expression levels of the hepatic TG synthases FAS and ACC and downregulated the expression levels of the hepatic TG synthesis proteins SREBP-1 and ChREBP. Moreover, it significantly upregulated the expression level of SIRT1 and downregulated the expression level of AMPK. Conclusion Fructus Trichosanthis-macrostem onion can regulate blood lipid levels in hyperlipidemia mice possibly by activating the SIRT1/AMPK pathway and inhibiting the expression of proteins and synthases associated with hepatic TG synthesis and the endogenous synthesis of TG.
作者
刘洁
王雨婷
李正龙
张文龙
许添阳
谢宜瑜
王清萍
陈颖
吴冰雨
吴鸿飞
LIU Jie;WANG Yuting;LI Zhenglong;ZHANG Wenlong;XU Tianyang;XIE Yiyu;WANG Qingping;CHEN Ying;WU Bingyu;WU Hongfei(Anhui Province Key Laboratory of Research&Development of Chinese Medicine,School of Pharmacy,Anhui University of Chinese Medicine,Anhui Hefei 230012,China)
出处
《安徽中医药大学学报》
CAS
2023年第6期59-65,共7页
Journal of Anhui University of Chinese Medicine
基金
安徽省自然科学基金项目(2208085MH275)
安徽高校自然科学研究项目(KJ2021A0592)
安徽省大学生创新创业基金(S202110369032,S202110369046)。
关键词
瓜蒌
薤白
三酰甘油
脂肪合成
信号通路
SIRT1
AMPK
Fructus Trichosanthis
Macrostem onion
Triglyceride
Fat synthesis
Signaling pathway
Silent information regulator 1
AMP-activated protein kinase