茯苓杏仁甘草汤调控巨噬细胞极化抑制动脉粥样硬化病变的进展  

Fuling Xingren Gancao granules regulate macrophage polarization and inhibit the progression of atherosclerosis

作　　者：彭超杰 南淞华 吴林柯 孟雪 吴鸿[1,2] PENG Chaojie;NAN Songhua;WU Linke;MENG Xue;WU Hong(the Second Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450002,China;Institute of Cardiovascular Disease,Henan University of Chinese Medicine,Zhengzhou 450002)

机构地区：[1]河南中医药大学第二附属医院,郑州450002 [2]河南中医药大学心血管病研究所,郑州450002

出　　处：《中国比较医学杂志》2024年第10期38-46,共9页Chinese Journal of Comparative Medicine

基　　金：河南省自然基金面上项目(232300420054);河南省科技研发计划联合基金(222301420088);河南省高校重点科研项目(23A360013)。

摘　　要：目的 探讨茯苓杏仁甘草汤(Fuling Xingren Gancao granule, FXG)对小鼠动脉粥样硬化(atherosclerosis, AS)巨噬细胞极化的调控作用。方法 ApoE-/-小鼠构建AS模型,RAW264.7巨噬细胞构建极化模型。油红O和苏木精-伊红染色法(hematoxylin-eosin staining, HE)观察主动脉斑块总面积和主动脉管腔狭窄程度。荧光定量PCR和Western blot体内外检测M1型极化因子诱导型一氧化氮合酶(inducible nitric oxide synthase, iNOS)、单核细胞趋化蛋白1(monocyte chemotactic protein 1,CCL2)和M2型极化因子精氨酸酶-1(arginase-1,Arg-1)、类几丁质酶样蛋白(chitinase-like protein 3,YM1)、甘露糖受体(CD206)的表达水平及信号转导和转录激活因子3(signal transducer and activator of transcription, STAT3)磷酸化水平。结果 FXG明显减少ApoE-/-小鼠主动脉斑块总面积、降低M1型巨噬细胞极化因子iNOS、CCL2表达水平,升高M2型巨噬细胞极化因子Arg-1、YM1表达水平(P<0.05)。模型组小鼠和M1型巨噬细胞STAT3磷酸化水平降低,在FXG干预后其磷酸化水平上调(P<0.05)。P-STAT3抑制剂Stattic部分消除了FXG对iNOS和Arg-1的调控作用(P<0.05)。结论 FXG具有抑制AS进展的作用,其作用与靶向STAT3调控巨噬细胞极化有关。Objective To investigate the regulatory effect of Fuling Xingren Gancao granules(FXG)on macrophage polarization in atherosclerosis(AS)model mice.Methods ApoE~(-/-)mice were used to construct an AS model and RAW264.7 macrophages were used to construct a polarized cell model.The total area of aortic plaques and the degree of aortic stenosis were detected by Oil red O and hematoxylin and eosin staining,respectively.Expression levels of the M1 polarization factors inducible nitric oxide synthase(iNOS)and chemokine ligand 2(CCL2),as well as the M2 macrophage factors Arg-1,YM1,and CD206,and the phosphorylation levels of signal transducer and activator of transcription(STAT3)in vitro and in vivo were detected by polymerase chain reaction and Western blot.Results FXG significantly reduced the total area of aortic plaques in ApoE~(-/-)mice,decreased the expression levels of the M1 macrophage polarization factors iNOS and CCL2,and increased the expression levels of the M2 macrophage polarization factors Arg-1 and YM1(P<0.05).STAT phosphorylation levels were decreased in the model mice and M1 macrophages,but were upregulated after FXG intervention(P<0.05).The STAT3 inhibitor Stattic partially eliminated the regulatory effect of FXG on iNOS and Arg-1(P<0.05).Conclusions FXG has an inhibitory effect on the progression of AS,via targeting STAT3 to regulate macrophage polarization.

关 键 词：茯苓杏仁甘草汤 动脉粥样硬化 巨噬细胞极化 信号转导和转录激活因子3 

分 类 号：R-33[医药卫生]