健脾化瘀祛痰法对apoA-Ⅰ/AMPK/CPT1A信号通路介导的脂肪酸β氧化改善血脂异常的调控作用及其机制  

Regulatory effect of Jianpi Huayu Qutan method on dyslipidemia improved by fatty acidβoxidation mediated by apoA-Ⅰ/AMPK/CPT1A signaling pathway and its mechanism

作　　者：张琦[1] 赵秋宇[1] 隋国媛 刘慧慧[2] 翟亚荣 于宁[1] 王杰[1] 裘雪莹 孟嘉伟 贾连群[1] ZHANG Qi;ZHAO Qiuyu;SUI Guoyuan;LIU Huihui;ZHAI Yarong;YU Ning;WANG Jie;QIU Xueying;MENG Jiawei;JIA Lianqun(Ministry of Education Key Laboratory of Visceral Phenomenon Theory and Application in Traditional Chinese Medicine,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;College of Integrated Traditional Chinese and Western Medicine,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学中医脏象理论及应用教育部重点实验室,辽宁沈阳110847 [2]辽宁中医药大学中西医结合学院,辽宁沈阳110847

出　　处：《吉林大学学报（医学版）》2022年第6期1395-1402,共8页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金项目(82074145);辽宁省自然科学基金项目(2019-ZD-0436);辽宁省“兴辽英才计划”项目(XLYC1902100)。

摘　　要：目的:探讨健脾化瘀祛痰法对高脂血症大鼠血脂异常的影响,基于载脂蛋白AⅠ(apoA-Ⅰ)/单磷酸腺苷激活蛋白激酶(AMPK)/肉毒碱棕榈酰转移酶ⅠA(CPT1A)信号通路阐明其分子机制。方法:32只大鼠随机分为空白对照组、模型组、辛伐他汀组(给予1.575 mg·kg^(-1)·d^(-1)辛伐他汀)和化瘀祛痰方(HYQTP)组(给予13.846 mg·kg^(-1)·d^(-1)化瘀祛痰方药物),每组8只。空白对照组大鼠给予正常饮食,模型组、辛伐他汀组和HYQTP组大鼠给予高脂饲料,建立高脂血症大鼠模型。8周后,辛伐他汀组和HYQTP组大鼠灌胃相应药物;空白对照组和模型组大鼠给予等体积生理盐水。全自动生化分析仪检测各组大鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-c)和高密度脂蛋白胆固醇(HDL-c)水平,HE染色观察各组大鼠肝组织病理形态表现,油红O染色观察各组大鼠肝组织脂质沉积情况,检测各组大鼠肝组织中TG水平,ELISA法检测各组大鼠肝组织中apoA-Ⅰ水平,实时荧光定量PCR(RT-qPCR)法检测各组大鼠肝组织中apoA-Ⅰ、B族Ⅰ型清道夫受体(SR-B1)和CPT1A mRNA表达水平,Western blotting法检测各组大鼠肝组织中高密度脂蛋白受体(SR-B1)、AMPK、磷酸化AMPK(p-AMPK)和CPT1A蛋白表达水平。结果:与空白对照组比较,模型组大鼠血清TC、TG和LDL-c水平升高(P<0.05),HDL-c水平降低(P<0.05);肝组织中TG水平升高(P<0.05);肝细胞出现明显肿胀,体积增大;并且可见明显红色脂滴分布;肝组织中apoA-Ⅰ、SR-B1和CPT1A mRNA及蛋白表达水平降低(P<0.05),p-AMPK/AMPK比值降低(P<0.05);与模型组比较,辛伐他汀组和HYQTP组大鼠血清TC、TG和LDL-c水平降低(P<0.05),HDL-c水平升高(P<0.05);肝组织中TG水平降低(P<0.05);肝细胞肿胀明显减轻,脂滴分布明显减少,肝组织中apoA-Ⅰ、SR-B1和CPT1A mRNA及蛋白表达水平升高(P<0.05),p-AMPK/AMPK比值升高(P<0.05)。结论:健脾化瘀祛痰法能够改善高脂血症�Objective:To explore the effect of the Jianpi Huayu Qutan method on the dyslipidemia in the rats and to elucidate its molecular mechanism based on apolipoprotein A-Ⅰ(apoA-Ⅰ)/adenosine monophosphate activated protein kinase(AMPK)/carnitine palmitoyltransferaseⅠA(CPT1A)signaling pathway.Methods:A total of 32 rats were randomly divided into blank control group,model group,simvastatin group(given 1.575 mg·kg^(-1)·d^(-1) simvastatin)and Huayu Qutan Prescription(HYQTP)group(given 13.846 mg·kg^(-1)·d^(-1) HYQTP drug),and there were 8 rats in each group.The rats in blank control group were given normal diet,and the rats in model group,simvastatin group and HYQTP group were given high-fat diet to establish the hyperlipidemia rat models.After 8 weeks,the rats in simvastatin group and HYQTP group were given drugs by gavage;the rats in blank control group and model group were given the same volume of normal saline.The levels of total cholesterol(TC),triglycerides(TG),low density lipoprotein cholesterol(LDL-c)and high density lipoprotein cholesterol(HDL-c)in serum of the rats in various groups were detected by automatic biochemical analyzer;HE staining was used to observe the pathomorphology of liver tissue of the rats in various groups;Oil red O staining was used to observe the lipid deposition in liver tissue of the rats in various group;the levels of TG in liver tissue of the rats in various groups were detected;ELISA method was used to detect the levels of apoA-Ⅰin liver tissue of the rats in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of apoA-Ⅰ,scavenger receptor class B type 1(SR-B1),and CPT1A mRNA in liver tissue of the rats in various groups;Western blotting method was used to detect the expression levels of SR-B1,phosphorylated AMPK(p-AMPK)and CPT1A proteins in liver tissue of the rats in various groups.Results:Compared with blank control group,the levels of serum TC,TG,and LDL-c of the rats in model group were increased(P<0.05),and the

关 键 词：血脂异常 脂肪酸β氧化 载脂蛋白AⅠ 单磷酸腺苷激活蛋白激酶 肉毒碱棕榈酰转移酶ⅠA 

分 类 号：R255.7[医药卫生—中医内科学]