健脾祛痰方调节M1/M2巨噬细胞极化改善动脉粥样硬化的实验研究  

Experimental study on Jianpi Qutan Formula regulating M1/M2 macrophage polarization to improve atherosclerosis

作　　者：韩晓萌 刘悦[1,2] 赵誉 于茂生 谭咪 HAN Xiao-meng;LIU Yue;ZHAO Yu;YU Mao-sheng;TAN Mi(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110000,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847 [2]辽宁中医药大学附属医院,辽宁沈阳110000

出　　处：《中国中药杂志》2025年第6期1610-1617,共8页China Journal of Chinese Materia Medica

基　　金：辽宁省自然科学基金优秀青年基金计划项目(2023JH3/10200016);国家自然科学基金项目(81703970)。

摘　　要：探究健脾祛痰方通过磷酸化激活信号传导和转录激活因子(signal transducer and activator of transcription,STAT)6调节动脉粥样硬化(atherosclerosis,AS)斑块中经典活化型巨噬细胞(classically activated macrophages,M1)/替代活化型巨噬细胞(alternatively activated macrophages,M2)平衡,减轻炎症反应,提高斑块稳定性,而发挥抗AS的作用机制。采用AS饲料喂养载脂蛋白E(apolipoprotein E,ApoE)^(-/-)小鼠8周建立AS模型,按照随机数字表法将ApoE^(-/-)小鼠分为模型组(Mod组)、健脾祛痰方组(JPQT组,8.97 g·kg^(-1))和阿托伐他汀钙片组(ATO组,1.3 mg·kg^(-1)),每组10只。另设10只以普通饲料喂养的相同周龄雄性C57BL/6J小鼠为空白组(Con组)。JPQT组和ATO组连续灌胃给药8周,Con组和Mod组给予等量生理盐水灌胃。持续监测小鼠体质量,取血后比较各组小鼠血清总胆固醇(total cholesterol,TC)和甘油三酯(triglyceride,TG)水平。苏木素-伊红(hematoxylin-eosin,HE)染色、油红O染色观察主动脉组织斑块形成情况;酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)检测促炎因子白细胞介素(interleukin,IL)-6、IL-12和抗炎因子IL-10的表达水平;免疫荧光检测主动脉分化簇(cluster of differentiation,CD)86和CD206的阳性表达;Western blot检测主动脉诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、精氨酸酶1(arginase 1,Arg1)、STAT6及p-STAT6的蛋白表达水平。与Con组相比,Mod组小鼠体质量和血脂水平增加,主动脉结构紊乱,有明显AS斑块形成,并伴随大量脂质沉积,血清促炎因子IL-6、IL-12水平以及CD86、iNOS蛋白水平显著上升,血清抗炎因子IL-10水平以及CD206、Arg1、p-STAT6/STAT6水平显著降低;与Mod组比较,各药物干预组小鼠体质量、血脂代谢情况均得到改善,主动脉结构改善较为明显,脂质堆积减少,血清促炎因子IL-6、IL-12水平以及CD86、iNOS蛋白水平显著下降,血清抗炎因子IL-10水平以及CD206、To investigate the mechanism of Jianpi Qutan Formula in regulating the balance between classically activated macrophages(M1)and alternatively activated macrophages(M2)in atherosclerotic plaques through phosphorylation and activation of the signal transducer and activator of transcription 6(STAT6),thereby reducing inflammation,increasing plaque stability,and exerting anti-atherosclerosis(AS)effects.An AS model was established by feeding apolipoprotein E(ApoE)^(-/-)mice with atherosclerotic chow for 8 weeks.The ApoE^(-/-)mice were randomly divided into a model group(Mod group),a Jianpi Qutan Formula group(JPQT group,8.97 g·kg^(-1)),and a Atorvastatin Calcium Tablets group(ATO group,1.3 mg·kg^(-1))according to a random table method,with 10 mice in each group.Additionally,10 male C57BL/6J mice of the same age,fed with a normal diet,were set as the control group(Con group).The JPQT and ATO groups received their respective treatments via oral gavage for 8 consecutive weeks,while the Con and Mod groups were administered an equivalent volume of saline.Body weight was continuously monitored,and after blood collection,total cholesterol(TC)and triglyceride(TG)levels in the serum of each group were compared.Hematoxylin-eosin(HE)staining and oil red O staining were used to observe plaque formation in aortic tissue.Enzyme-linked immunosorbent assay(ELISA)was employed to detect the expression levels of pro-inflammatory cytokines interleukin(IL)-6 and IL-12,as well as the anti-inflammatory cytokine IL-10.Immunofluorescence was used to detect the positive expression of aortic cluster of differentiation(CD)86 and CD206.Western blot analysis was conducted to detect the protein expression levels of aortic inducible nitric oxide synthase(iNOS),arginase 1(Arg1),STAT6,and p-STAT6.Compared to the Con group,the Mod group exhibited increased body weight and blood lipid levels,disordered aortic structure,significant AS plaque formation accompanied by extensive lipid deposition,and elevated serum levels of pro-inflammatory cytokines IL-6

关 键 词：动脉粥样硬化 STAT6 健脾祛痰方 巨噬细胞极化 

分 类 号：R285.5[医药卫生—中药学]