Panax Notoginseng Saponins Inhibits Ventricular Remodeling after Myocardial Infarction in Rats Through Regulating ATF3/MAP2K3/p38 MAPK and NFκB Pathway

Objective:To explore whether Panax notoginseng saponins(PNS)exhibits heart protective effect in myocardial infarction(MI)rats and to identify the potential signaling pathways involved.Methods:MI rats induced by ligating the left anterior descending(LAD)coronary artery were assigned to sham coronary artery ligation or coronary artery ligation.Totally 36 Sprague-Dawley rats were randomly divided into sham group(distilled water,n=9),MI group(distilled water,n=9),PNS group(PNS,40 mg/kg daily,n=9)and fosinopril group(FIP,1.2 mg/kg daily,n=9)according to a random number table.The left ventricular morphology and function were conducted by echocardiography.Histological alterations were evaluated by the stainings of HE and Masson.The serum levels of C reactive protein(CRP),tumor necrosis factorα(TNF-α),growth differentiation factor-15(GDF-15)and the ratio of metalloproteinase-9(MMP-9)and tissue inhibitor of MMP-9(TIMP-1)were determined by ELISA.The levels of activating transcription factor 3(ATF3),mitogen-activated protein kinase kinase 3(MAP2 K3),p38 mitogen-activated protein kinase(p38 MAPK),phosphorylation of p38 MAPK(p-p38 MAPK),transforming growth factor-β(TGF-β1),collagenⅠ,nuclear factor kappa B p65(NFκB p65),phosphorylation of NFκB p65(p-NFκB p65),and phosphorylation of inhibitory kappa Bα(p-IκBα)in hearts were measured by Western blot and immunohistochemical staining,respectively.Results:PNS improved cardiac function and fibrosis in MI rats(P<0.05).The serum levels of CRP,TNF-α,GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI rats.The expressions of TGF-β1,collagenⅠ,MAP2 K3,p38 MAPK,p-p38 MAPK,NFκB p65,p-NFκB p65,and p-IκBαwere down-regulated,while ATF3 increased with the treatment of PNS(P<0.05).Conclusions:PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2 K3/p38 MAPK and NFκB signaling pathways.These results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.

化浊祛湿通心方对心肌梗死大鼠肠道菌群的调节及功能基因预测

目的:探讨化浊祛湿通心方调理脾胃治疗冠状动脉粥样硬化性心脏病(冠心病)的可能机制。方法:采用冠状动脉左前降支结扎复制冠心病大鼠模型,采用福辛普利为阳性对照药,化浊祛湿通心方自造模之日起连续给药30d。多普勒超声心动法检测心功能,HE染色观察心脏梗死面积和形态学变化,16S rRNA V3~V4区Illumina测序和多变量统计方法分析肠道菌群的丰度变化,隐性状态重建进行功能基因预测。结果:化浊祛湿通心方能显著改善冠心病大鼠的心功能,增加肠道有益菌群乳酸杆菌科乳酸杆菌的数量(P<0.05),减少致病菌变形菌纲、毛螺菌科、消化链球菌科、罗氏菌属的数量(P<0.05)。通过功能预测分析发现化浊祛湿通心方主要调节精氨酸-脯氨酸代谢通路。结论:化浊祛湿通心方具有改善心肌梗死大鼠心脏结构和功能的作用。该作用可能与其调整肠道乳酸菌/变形菌菌群失衡和改善心肌能量代谢相关。