摘要
目的:研究黄连解毒汤对动脉粥样硬化(AS)模型小鼠M1、M2型巨噬细胞极化的调控作用,初步阐明其防治AS的机制。方法:将60只雄性ApoE^(-/-)小鼠随机分为空白对照组、模型组、辛伐他汀组[阳性对照,5 mg/(kg·d)]和黄连解毒汤低、中、高剂量组[5、10、20 mg/(kg·d),以生药总量计],每组10只。除空白对照组外,其余各组小鼠均饲以高脂饲料复制AS模型。造模结束后,各药物组小鼠灌胃相应药液,空白对照组和模型组小鼠灌胃生理盐水。每天给药1次,连续4周。给药结束后,采用全自动生化仪检测小鼠血清中三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)含量,采用天狼猩红染色法观察小鼠主动脉胶原纤维形成情况,采用酶联免疫吸附测定法检测小鼠血清中诱导型一氧化氮合酶(iNOS)、甘露糖受体(CD206)含量,采用实时荧光定量-聚合酶链式反应法检测小鼠主动脉中白细胞介素1β(IL-1β)、iNOS、肿瘤坏死因子α(TNF-α)、IL-10、类几丁质酶3样分子(YM1)、炎症区域分子1(Fizz1)mRNA的表达水平。结果:与空白对照组比较,模型组小鼠血清中TC、TG、LDL-C、iNOS含量以及主动脉中IL-1β、iNOS、TNF-αmRNA的表达水平均显著升高(P<0.05或P<0.01),血清中HDL-C、CD206含量以及主动脉中IL-10、YM1、Fizz1 mRNA的表达水平均显著降低(P<0.01);主动脉血管内皮下可见厚厚一层胶原纤维。与模型组比较,各药物组小鼠上述血清指标均显著改善(P<0.05或P<0.01);且黄连解毒汤中、高剂量组小鼠主动脉中IL-1β、TNF-α、iNOS mRNA的表达水平均显著降低(P<0.05或P<0.01),IL-10、YM1、Fizz1 mRNA的表达水平均显著升高(P<0.05或P<0.01),且其血管内皮相对光滑。结论:黄连解毒汤可通过抑制M1型巨噬细胞极化、促进M2型巨噬细胞极化,减少炎症反应,维持动脉内粥样斑块的稳定性,从而发挥抗AS的作用。
OBJECTIVE:To study the regulation effects of Huanglian jiedu decoction on M1 and M2 macrophage polarization in atherosclerosis(AS)model mice,and to elucidate its mechanism of AS prevention and treatment.METHODS:Sixty ApoE^(-/-)male mice were randomly divided into blank control group,model group,simvastatin group[positive control,5 mg/(kg·d)],Huanglian jiedu decoction low-dose,medium-dose and high-dose groups[5,10,20 mg/(kg·d),by crude drug],with 10 mice in each group.Except for blank control group,other groups were given high-fat diet to induce AS model.After modeling,administration groups were given relevant medicine intragastrically;blank control group and model group were given normal saline intragastrially,once a day,for consecutive 4 weeks.After medication,the contents of triglyceride(TG),total cholesterol(TC),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)in serum were detected by automatic biochemical analyzer.Sirius red staining was used to observe the formation of collagen fibers in the aorta of mice.The serum contents of iNOS and CD206 were determined by ELISA.mRNA expression levels of IL-1β,iNOS,TNF-α,YM1 and Fizz1 in the aorta were detected by RT-PCR.RESULTS:Compared with blank control group,the serum contents of TC,TG,LDL-C and iNOS,mRNA expression levels of IL-1β,iNOS,TNF-αin the aorta were significantly increased in model group(P<0.05 or P<0.01),while the serum contents of HDL-C and CD206 and mRNA expression levels of IL-10,YM1,Fizz1 in the aorta were significantly decreased(P<0.01).There was a thick layer of collagen fibers under the endothelium of aorta.Compared with model group,above serum indexes of mice were improved significantly in administration groups(P<0.05 or P<0.01);mRNA expression levels of IL-1,iNOS and TNF-αin the aorta in Huanglian jiedu decoction medium-dose and high-dose groups were decreased significantly(P<0.01),while mRNA expression levels of IL-10,YM1 and Fizz1 were increased significantly(P<0.05 or P<0.01).The vascular endothelium was relatively smooth.CONCLUSIONS:Huanglian jiedu decoction can inhibit the polarization of M1 macrophages and promote the polarization of M2 macrophages,reduce the inflammatory reaction,maintain the stability of atherosclerotic plaque in artery,so as to play the role of anti-AS.
作者
李弼仁
李海怡
朱泳
罗川晋
LI Biren;LI Haiyi;ZHU Yong;LUO Chuanjin(Emergency Department,Hainan Provincial Hospital of TCM,Haikou 570100,China;The First Clinical Medical College,Guangzhou University of TCM,Guangzhou 510405,China;Dept.of Cardiovascular Disease,the First Affiliated Hospital of Guangzhou University of TCM,Guangzhou 510405,China)
出处
《中国药房》
CAS
北大核心
2021年第8期939-944,共6页
China Pharmacy
基金
国家自然科学基金资助项目(No.81673923)
广东省普通高校重点科研平台和科研项目(No.2018KQNCX043)。
关键词
黄连解毒汤
动脉粥样硬化
巨噬细胞极化
小鼠
Huanglian jiedu decoction
Atherosclerosis
Macrophage polarization
Mice
