黄连-花椒提取液对高脂血症小鼠的作用和机制研究  

Study on the Effect and Mechanism of Huanglian-SichuanPepper Extract on Hyperlipidemic Mice

作　　者：苗青[1] 刘燕君 王瑞海[1] 刘丽梅[1] 胡镜清 MIAO Qing;LIU Yanjun;WANG Ruihai;LIU Limei;HU Jingqing(Institute of Basic Theory for Chinese Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;China Science and Technology Development Center for Chinese Medicine,Beijing 100027,China)

机构地区：[1]中国中医科学院中医基础理论研究所,北京100700 [2]中国中医药科技发展中心,北京100027

出　　处：《中国中医基础医学杂志》2024年第10期1715-1720,共6页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：中国博士后科学基金项目(2018T110190,2017M610153);中央级公益性科研院所基本科研业务费专项(YZ-1671)。

摘　　要：目的基于寒热并用法研究黄连-花椒提取液对高脂血症的作用与可能的机制。方法采用高脂喂养ApoE-/-小鼠建立高脂血症模型,给予黄连-花椒提取液进行干预。全自动生化仪检测各组小鼠血清总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、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)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、肿瘤坏死因子(tumor necrosis factor,TNF)-α、白介素(interleukin,IL)-1β和IL-6水平;HE染色和油红O染色观察肝组织病理变化;ELISA、RT-qPCR法检测肝脏3-羟基-3-甲基戊二酸单酰辅酶A(3-hydroxy-3-methyl glutaryl coenzyme A reductase,HMG-CoA)还原酶水平和mRNA表达;Western blot检测细胞外信号调节激酶/p38丝裂原活化蛋白激酶(extracellular signal-regulated kinase/p38 mitogen activated protein kinase,ERK/p38 MAPK)信号通路相关蛋白含量。结果黄连-花椒干预后,小鼠血清中TC、TG、LDL-C、ALT、AST、TNF-α、IL-1β和IL-6水平均显著降低(P<0.05);肝细胞脂肪空泡和脂质沉积减少,肝脂肪病变减轻;肝脏HMG-CoA还原酶水平和mRNA表达显著下降(P<0.01),p-ERK1/2/ERK1/2和p-p38/p38均显著降低(P<0.01)。结论黄连-花椒提取液可降低高脂血症小鼠血脂水平,减轻肝脂肪病变,通过抑制肝脏HMG-CoA还原酶减少胆固醇合成,降低炎症因子水平,其机制可能与调控ERK/p38 MAPK信号通路有关。Objective To investigate the effect and possible mechanism of the compatibility of Huanglian-Sichuan Pepper extract on hyperlipidemia mice.Methods ApoE-/-mice were fed with high fat to establish hyperlipidemia model and treated with Huanglian-Sichuan Pepper extract.The serum levels of TC,TG,LDL-C,HDL-C,ALT,AST,TNF-α,IL-1βand IL-6 were detected by automatic biochemical analyzer.HE staining or oil red O staining were used to observe the pathological changes of liver tissue of mice.ELISA and RT-qPCR were used to detect the level and mRNA expression of HMG-CoA reductase in the liver.Western blot was used to detect the related protein expression of ERK/p38 MAPK signaling pathway.Results After administration,the levels of TC,TG,LDL-C,ALT,AST,TNF-α,IL-1βand IL-6 in the serum of mice were significantly decreased(P<0.05),hepatocyte fat vacuoles and lipid deposition were reduced,and hepatic steatosis was alleviated,the activity and expression of HMG-CoA reductase in liver were significantly decreased(P<0.01),the expression of p-ERK1/2/ERK1/2 and p-p38/p38 were significantly decreased(P<0.01).Conclusion The compatibility of Huanglian-Sichuan Pepper extract can reduce the blood lipid level,alleviate hepatic steatosis of hyperlipidemia mice.It can still inhibit the hepatic HMG-CoA reductase to reduce cholesterol synthesis and inhibit the expression of inflammatory factors.The mechanism may be related with regulating the ERK/p38 MAPK signaling pathway.

关 键 词：寒热并用法 黄连-花椒提取液 高脂血症 HMG-COA还原酶 ERK/p38 MAPK信号通路 

分 类 号：R285[医药卫生—中药学]