目的:探讨抗纤益心方调节单核细胞趋化蛋白-1(monocyte chemotactic protein-1，MCP-1)/趋化因子C-C-基元受体2(C-C-subunit receptor 2，CCR2)信号通路对扩张型心肌病(dilated cardiomyopathy，DCM)大鼠心功能的影响。方法:取SD雄性大鼠随机分为对照组、模型组、抗纤益心方(18。8g·kg-1)组、抗纤益心方(18。8g·kg-1)+空载(空载质粒)组、抗纤益心方(18。8g·kg-1)+MCP-1过表达(MCP-1 过表达质粒)组，模型组和给药干预组大鼠以腹腔注射阿霉素法诱导建立DCM模型，对照组大鼠于腹腔内注射等剂量生理盐水，以抗纤益心方(每天1次)和质粒(每周2次)分组干预3周后检测各组大鼠心功能指标左室舒张末期内径(left ventricular end diastolic diameter，LVEDD)、左室收缩末期内径(left ventricular end systolic diam-eter，LVESD)、左心射血分数(left ventricular ejection fraction，LVEF)、左室短轴缩短率(left ventricular short axis shortening rate，FS)、心脏指数、心肌组织病理形态及纤维化、血清肿瘤坏死因子α(TNF-α)、转化生长因子β1(TGF-β1)及MCP-1水平、心肌组织胶原[Ⅰ型胶原蛋白(Col-Ⅰ)、Ⅲ型胶原蛋白(Col-Ⅲ)、α平滑肌肌动蛋白(α-SMA)]生成及MCP-1/CCR2通路相关蛋白表达。结果:与对照组相比，模型组大鼠心肌组织发生严重损伤，心脏指数、LVEDD、LVESD、胶原容积分数(CVF)、血清TNF-α、TGF-β1 及MCP-1 水平，心肌组织 Col-Ⅰ、Col-Ⅲ、α-SMA、MCP-1、CCR2蛋白表达显著升高(P＜0。05)，LVEF、FS显著降低(P＜0。05)。与模型组比较，抗纤益心方组大鼠心肌组织损伤减轻，心脏指数、LVEDD、LVESD、CVF、血清TNF-α、TGF-β1及MCP-1 水平，心肌组织Col-Ⅰ、Col-Ⅲ、α-SMA、MCP-1、CCR2蛋白表达降低(P＜0。05)，LVEF、FS升高(P＜0。05);抗纤益心方+空载组大鼠各指标无明显变化(P＞0。05)。过表达MCP-1可减弱抗纤益心方对DCM大鼠各指标的影响。结论:抗纤益心方可通过降低MCP-1/CCR2信号通路活性而抑制DCM大鼠炎症，进而减轻大鼠心肌损伤及纤维化，改善其心功能。
Effects of Kangxian Yixin Formula on cardiac function of rats with dilated cardiomyopathy via regulating MCP-1/CCR2 signaling pathway
OBJECTIVE To investigate the effects of Kangxian Yixin Formula on cardiac function of rats with dilated cardio-myopathy(DCM)by modulating monocyte chemotactic protein-1(MCP-1)/chemokine C-C-subunit receptor 2(CCR2)signal-ing pathway.METHODS SD male rats were randomly divided into five groups:control group,model group,Kangxian Yixin Formula(18.8 g·kg-1)group,Kangxian Yixin Formula(18.8 g·kg-1)+empty(empty plasmid)group,and Kangxian Yixin Formula(18.8 g·kg-1)+MCP-1 overexpression(MCP-1 overexpression plasmid)group.The model group and intervention groups were induced to develop a DCM model by intraperitoneal injection of doxorubicin,while the control group received an equal dose of saline intraperitoneally.After 3 weeks of daily intervention with Kangxian Yixin Formula and twice-a-week plasmid intervention,cardiac function parameters were measured,including left ventricular end diastolic diameter(LVEDD),left ven-tricular end systolic diameter(LVESD),left ventricular ejection fraction(LVEF),left ventricular short axis shortening rate(FS),heart index,myocardial tissue pathology and fibrosis,serum levels of tumor necrosis factor-α(TNF-α),transforming growth factor-β1(TGF-β1),and MCP-1,as well as the expression of collagen production(type Ⅰ collagen(Col-Ⅰ),type Ⅲcollagen(Col-Ⅲ),α-smooth muscle actin(α-SMA)and MCP-1/CCR2 pathway related proteins in myocardial tissue of rats in each group.RESULTS Compared with the control group,the model group exhibited severe myocardial tissue damage,and sig-nificant increase in heart index,LVEDD,LVESD,collagen volume fraction(CVF),serum levels of TNF-α,TGF-β1,and MCP-1,and expression of myocardial tissue Col-Ⅰ,Col-Ⅲ,α-SMA,MCP-1,and CCR2 proteins(P＜0.05),along with a significant decrease in LVEF and FS(P＜0.05).Compared with the model group,the Kangxian Yixin Formula group showed reduced myocardial tissue damage,decreased cardiac index,LVEDD,LVESD,CVF,serum TNF-α,TGF-β1,and MCP-1,and expression of myocardial tissue Col-Ⅰ,Col-Ⅲ,α-SMA,MCP-1,and CCR2 proteins(P＜0.05),with an increase in LVEF and FS(P＜0.05).There was no obvious change in any indicators in the Kangxian Yixin Formula+empty group(P＞0.05).Overexpression of MCP-1 could weaken the effects of Kangxian Yixin Formula on various indicators in DCM rats.CONCLUSION Kangxian Yixin Formula can inhibit inflammation in DCM rats by reducing the activity of MCP-1/CCR2 signal-ing pathway,thereby alleviating myocardial injury and fibrosis in rats and improving their cardiac function.
Kangxian Yixin FormulaMCP-1/CCR2dilated cardiomyopathycardiac function
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