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脂必泰调控PPARγ/CD36通路抗动脉粥样硬化的实验研究OA

Experimental Study on Anti-atherosclerotic Effect of Zhibitai Capsule Regulating PPARγ/CD36 Pathway

中文摘要英文摘要

目的:基于过氧化物酶体增殖物激活受体 γ(peroxisome proliferator-activated receptor γ,PPARγ)/白细胞分化抗原 36(cluster of differentiation 36,CD36)通路探讨脂必泰调控小鼠动脉粥样硬化的作用机制.方法:36 只雄性 APOE-/-小鼠随机分为对照组(Control 组)、模型组(Model 组)、阿托伐他汀组(Atorvastatin 组,3 mg·kg-1)、脂必泰低剂量组(ZBT-L 组,31.2 mg·kg-1)、脂必泰中剂量组(ZBT-M 组,62.4 mg·kg-1)、脂必泰高剂量组(ZBT-H 组,124.8 mg·kg-1),每组 6 只.除 Control 组外,其余大鼠以高脂饲料喂养建立动脉粥样硬化模型,同时每日灌胃,连续12 周.采用 HE 染色、油红 O 染色观察小鼠主动脉病理形态和脂质蓄积情况;比色法测定血清总胆固醇(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)水平;ELISA 法检测血清氧化型低密度脂蛋白(oxidized LDL,ox-LDL)水平;Western blot 法检测主动脉 PPARγ、CD36 蛋白表达水平.结果:油红 O 染色显示,Control 组小鼠主动脉光滑平整,肝脏未见明显的红染脂滴;Model 组小鼠主动脉内膜可见明显的脂质红染,肝细胞可见较多的红染脂滴.HE 染色显示,Control 组小鼠主动脉各层结构正常;Model 组小鼠主动脉中膜结构紊乱,可见明显斑块;Atorvastatin 组小鼠主动脉结构紊乱,未见斑块形成;ZBT-H 组小鼠主动脉结构正常,管壁光滑.与 Control 组比较,Model 组小鼠主动脉脂质含量、主动脉与肝脏病变百分比升高(P<0.01);与 Model 组比较,Atorvastatin 组、ZBT-M 组及ZBT-H 组小鼠主动脉脂质含量、主动脉与肝脏病变百分比降低(P<0.05).与 Control 组比较,Model 组小鼠血清 TC、TG、LDL-C、ox-LDL 水平升高,HDL-C 水平降低(P<0.01);与 Model 组比较,Atorvastatin 组、ZBT-M 组及 ZBT-H 组小鼠血清 TC、TG、LDL-C、ox-LDL 水平降低,HDL-C 水平升高(P<0.05).与 Control 组比较,Model 组小鼠主动脉 PPARγ 蛋白表达水平降低,CD36 蛋白表达水平升高(P<0.01);与 Model 组比较,Atorvastatin 组、ZBT-M 组及 ZBT-H 组小鼠主动脉PPARγ 蛋白表达水平升高,CD36 蛋白表达水平降低(P<0.01).结论:脂必泰可预防动脉粥样硬化病变,其机制可能与调控PPARγ/CD36 信号通路,改善巨噬细胞脂质代谢有关.

Objective:To investigate the mechanism by which Zhibitai Capsule regulates atherosclerosis in mice based on the peroxisome proliferator-activated receptor γ(PPARγ)/cluster of differentiation 36(CD36)pathway.Methods:Thirty-six male APOE-/-mice were randomly divided into the control group(Control),model group(Model),atorvastatin group(Atorvastatin,3 mg·kg-1),Zhibitai low-dose group(ZBT-L,31.2 mg·kg-1),Zhibitai Capsule medium-dose group(ZBT-M,62.4 mg·kg-1),and Zhibitai high-dose group(ZBT-H,124.8 mg·kg-1),with 6 mice in each group.Except for the Control group,the remaining mice were fed a high-fat diet to establish the atherosclerosis model and were administered orally once daily for 12 consecutive weeks.Hematoxylin-e-osin(HE)staining and Oil Red O staining were used to observe aortic pathological morphology and lipid accumulation in mice;the col-orimetric method was used to determine serum levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C);ELISA was employed to detect serum oxidized low-density lipopro-tein(ox-LDL)levels;and Western blot was used to assess aortic PPARγ and CD36 protein expression levels.Results:Oil Red O stai-ning showed that the aorta of mice in the Control group was smooth,and no obvious red-stained lipid droplets were observed in the liv-er;in the Model group,obvious red-stained lipids were seen in the aortic intima,and more red-stained lipid droplets were observed in hepatocytes.HE staining showed that the structure of each layer of the aorta in the Control group was normal;in the Model group,the medial layer of the aorta was disordered,with obvious plaques visible;in the Atorvastatin group,the aortic structure was disordered,but no plaque formation was observed;in the ZBT-H group,the aortic structure was normal,with smooth vessel walls.Compared with the Control group,the Model group had increased aortic lipid content and higher percentages of lesions in the aorta and liver(P<0.01);compared with the Model group,the Atorvastatin group,ZBT-M group,and ZBT-H group had decreased aortic lipid content and lower percentages of lesions in the aorta and liver(P<0.05).Compared with the Control group,the Model group had increased serum levels of TC,TG,LDL-C,and ox-LDL,and decreased HDL-C levels(P<0.01);compared with the Model group,the Atorvastatin group,ZBT-M group,and ZBT-H group had decreased serum levels of TC,TG,LDL-C,and ox-LDL,and increased HDL-C levels(P<0.05).Compared with the Control group,the Model group had decreased aortic PPARγ protein expression and increased CD36 protein expression(P<0.01);compared with the Model group,the Atorvastatin group,ZBT-M group,and ZBT-H group had increased aor-tic PPARγ protein expression and decreased CD36 protein expression(P<0.01).Conclusion:Zhibitai Capsule can prevent atheroscle-rotic lesions,and its mechanism may be related to the regulation of the PPARγ/CD36 signaling pathway and the improvement of macro-phage lipid metabolism.

赵凤婷;麻京豫;孟徐兵;林锋

河南中医药大学第一临床医学院,河南 郑州 450000河南中医药大学第一附属医院/心脏中心/国家区域(中医)心血管诊疗中心,河南 郑州 450000河南中医药大学第一临床医学院,河南 郑州 450000河南中医药大学第一临床医学院,河南 郑州 450000

医药卫生

动脉粥样硬化脂必泰PPARγ/CD36 信号通路脂质代谢小鼠

atherosclerosisZhibitai CapsulePPARγ/CD36 signaling pathwaylipid metabolismmouse

《中医学报》 2026 (5)

1089-1095,7

河南省高等学校重点科研项目计划项目(23A320065)

10.16368/j.issn.1674-8999.2026.05.162

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