潜阳合剂激活STAT6促进巨噬细胞向修复型极化减轻心肌缺血再灌注损伤  

Qianyang Decoction attenuates myocardial ischemia reperfusion injury by promoting macrophages polarized toward reparative type via activating STAT6

作　　者：王婧 蔡婉[1] 王文瑾 葛文[1] 吴瑶瑶[1] 池浩[1] WANG Jing;CAI Wan;WANG Wenjin;GE Wen;WU Yaoyao;CHI Hao(Department of Cardiothoracic Surgery,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院心胸外科,上海201203

出　　处：《上海中医药大学学报》2025年第1期29-38,共10页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(82104787)。

摘　　要：目的:探讨潜阳合剂对小鼠心肌缺血再灌注(I/R)损伤的作用和机制。方法:40只C57BL/6雄性小鼠,分为假手术组(对照组)、模型组及潜阳合剂低、中、高剂量组(6.96、13.92、27.84 g/kg),每组8只。模型组及潜阳合剂各剂量组采用冠状动脉左前降支结扎的方法建立小鼠I/R模型,潜阳合剂各剂量组在造模前1 h灌胃干预1次。采用2,3,5-氯化三苯基四氮唑(TTC)染色比较各组心梗面积;乳酸脱氢酶(LDH)检测评价各组心肌损伤程度;苏木精伊红(H-E)染色检测各组心肌组织中炎性细胞浸润情况;酶联免疫吸附检测炎症因子表达;免疫荧光染色和蛋白免疫印记评价单核/巨噬细胞浸润情况和巨噬细胞极化情况。结果:高剂量潜阳合剂干预后心梗面积显著缩小(P<0.05)、LDH释放量显著减少(P<0.05),单核/巨噬细胞浸润数量显著减少(P<0.001),肿瘤坏死因子-α(TNF-α)、白介素(IL)-6和IL-1β表达显著降低(P<0.05)。免疫荧光和蛋白质免疫印迹(Western blot)结果显示,高剂量潜阳合剂干预后,巨噬细胞CD206表达显著上调(P<0.001),iNOS表达显著下调(P<0.001);高剂量潜阳合剂能够显著增加信号转导及转录激活蛋白6(STAT6)磷酸化(P<0.001)。结论:潜阳合剂可通过激活STAT6通路促进巨噬细胞向M2型极化,从而抑制I/R后炎症反应,减轻心肌I/R损伤。Objective:To explore the effect and mechanism of Qianyang Decoction on myocardial ischemia-reperfusion(I/R)injury in mice.Methods:A total of 40 male C57BL/6 mice were divided into sham group(control group),model group,and low,medium and high dose groups of Qianyang Decoction(6.96,13.92,27.84 g/kg),with 8 mice in each group.The model group and Qianyang Decoction each dose groups were subjected to ligation of the left anterior descending branch of the coronary artery to establish a mouse model of I/R injury.The Qianyang Decoction each dose groups were intragastrically intervened once 1 h before modeling.2,3,5-triphenyltetrazolium chloride(TTC)staining was used to compare the infarct of each group;lactate dehydrogenase(LDH)assay was used to evaluate the degree of myocardial injury in each group;hematoxylin-eosin(H-E)staining was used to detect inflammatory cell infiltration in myocardial tissue of each group;enzyme-linked immunosorbent assay was used to detect the expression of inflammatory factors;immunofluorescence staining and protein immunoblotting were used to evaluate the infiltration of monocytes/macrophages and the polarization of macrophages.Results:After the intervention of high dose Qiyang Decoction,myocardial infarction area was significantly reduced(P<0.05),lactate dehydrogenase release was significantly decreased(P<0.05),and the number of mononuclear/macrophage infiltrates were significantly decreased(P<0.05).The expression of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-1βwere significantly decreased(P<0.05).The results of immunofluorescence and immunoimprinting showed that the expression of CD206 was significantly up-regulated(P<0.001)and the expression of inducible nitric oxide synthase(iNOS)was significantly down-regulated(P<0.001)after the intervention of high dose Qiyang Decoction.The phosphorylation of signal transducer and activator of transcription 6(STAT6)was significantly increased by high dose of Qianyang Decoction(P<0.001).Conclusion:Qianyang Decoction can promote the polariz

关 键 词：潜阳合剂 炎症反应 巨噬细胞 极化 STAT6通路 

分 类 号：R285.5[医药卫生—中药学]