山东中医药大学学报2025，Vol.49Issue(2)：215-223,9.DOI:10.16294/j.cnki.1007-659x.2025.02.013
瓜蒌薤白半夏汤调控心脏FGF21因子干预冠心病痰浊壅塞证的机制研究
Mechanism of Gualou Xiebai Banxia Decoction(瓜蒌薤白半夏汤)Regulating Cardiac FGF21 in Intervention of Coronary Heart Disease with Pattern of Turbid Phlegm Obstruction
摘要
Abstract
Objective:To investigate the mechanism of Gualou Xiebai Banxia Decoction(瓜蒌薤白半夏汤)in the treatment of coronary heart disease with pattern of turbid phlegm obstruction(CHD-TZ).Methods:Seventy SD rats were fed adaptively for 1 week.Ten rats were randomly selected as the control group,and 10 rats underwent left anterior descending coronary artery ligation(LAD)as the common coronary heart disease(CHD)group.Fifty rats were given high fat emulsion(HEF)to establish hyperlipidemia model,and ten rats were selected as hyperlipidemia group.The other forty rats were divided into 4 groups,and LAD was performed after gavage of normal saline and different doses of Gualou Xiebai Banxia Decoction,respectively.The model of blockage of phlegm and turbidity in coronary heart disease was established.The rats with failed modeling were excluded,and were finally identified as control group,CHD group,hyperlipi-demia group,CHD-TZ group and Gualou Xiebai Banxia Decoction high-,medium-and low-dose(GXBD-H,GXBD-M,GXBD-L)groups,with 8 rats in each group.Myocardial infarction size was measured by 2,3,5-triphenyltetrazolium chloride(TTC)staining.Enzyme-linked immunosorbent assay(ELISA)was used to detect levels of plasma creatine kinase(CK),creatine kinase isoenzyme(CK-MB),four blood lipids[high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),total triglyceride(TG),total cholesterol(TC)]and fibroblast growth factor 21(FGF21).Western blot(WB)was used to detect the protein expression or phosphorylation level of myocardial tissue.Results:The myocardial infarction rate in CHD-TZ group was significantly higher than that in CHD group(P＜0.01).Compared with the CHD-TZ group,the myocardial infarction rates of the GXBD-H,GXBD-M,and GXBD-L groups were significantly decrease,and the differences were statistically significant(P＜0.01).The levels of CK and CK-MB in the CHD group were significantly higher than those in the control group,and the levels of CK and CK-MB in the CHD-TZ group were significantly higher than those in the CHD group,GXBD-H,GXBD-M,and GXBD-L groups(P＜0.01).Compared with the control group,the levels of TC,TG and LDL-C in the hyperlipidemia group and CHD-TZ group increased significantly,while the level of HDL-C decreased significantly(P＜0.01).The levels of TC,TG and LDL-C in the GXBD-H,GXBD-M and GXBD-L groups were lower than those in the CHD-TZ group,and the GXBD-M group had the lowest level(P＜0.01).The plasma level of FGF21 was significantly higher in the hyperlipidemia group than in the control group,higher in the CHD group than in the hyperlipidemia group(P＜0.01),and lower in the GXBD-M group than in the CHD-TZ group(P＜0.01).Western blotting results and relative quantitative data showed that the expression level of FGF21 in the heart of rats from low to high was the control group,the hyperlipidemia group,the CHD group,and the CHD-TZ group,and the expression level of FGF21 in the group of GXBD-M might decrease to the low level(P＜0.01).The expression level of fibroblast growth factor receptor 1(FGFR1)in the CHD group,CHD-TZ group and GXBD-M group was significantly higher than that in control group and hyperlipidemia group(P＜0.01).The expression level of βKlotho in the CHD group and CHD-TZ group increased significantly,and the expression level of βKlotho protein in the GXBD-M group was the highest(P＜0.01).Compared with the control group,the expression level of FRS2α in the CHD group increased significantly,and the expression level of FRS2α in the CHD group and GXBD-M group was higher than that in the CHD-TZ group(P＜0.01).The phosphorylation level of FRS2α protein in the CHD group was significantly higher than that in the control group,and it decreased significantly in the CHD-TZ group,and increased significantly in the GXBD-M group(P＜0.01).Conclusions:Gualou Xiebai Banxia Decoction can reverse the pathological changes of CHD-TZ significantly,which may reverse the lipid metabolism disorder of CHD-TZ by inducingβKlotho expression,activating FGF21/FGFR1/βKlotho-FRS2α signaling pathway and reducing cardiac FGF21 resistance while protecting the ischemic heart.关键词
瓜蒌薤白半夏汤/冠心病痰浊壅塞证/心肌缺血/高血脂/成纤维细胞生长因子21Key words
Gualou Xiebai Banxia Decoction(瓜蒌薤白半夏汤)/coronary heart disease with pattern of turbid phlegm obstruction/myocardial ischemia/hyperlipidemia/fibroblast growth factor 21分类
医药卫生引用本文复制引用
官帅,王海宇,孙滕,张志伟,赵启韬..瓜蒌薤白半夏汤调控心脏FGF21因子干预冠心病痰浊壅塞证的机制研究[J].山东中医药大学学报,2025,49(2):215-223,9.基金项目
国家自然科学基金项目(编号:81573852) （编号:81573852）
山东省自然科学基金项目(编号:ZR2021LZY042) （编号:ZR2021LZY042）
