麝香保心丸通过抑制TGF-β/Smad/ERK信号通路缓解急性心肌梗死大鼠心肌纤维化OA
Shexiang Baoxin pill alleviates myocardial fibrosis in rats with acute myocardial infarction by inhibiting TGF-β/Smad/ERK signaling pathway
目的 基于TGF-β/Smad/ERK信号通路探讨麝香保心丸(Shexiang Baoxin pill,SBP)对急性心肌梗死(AMI)大鼠心肌纤维化的影响.方法 48只雄性SD大鼠随机分为假手术组(sham组)、模型组、SBP低剂量组(L-SBP组)、SBP高剂量组(H-SBP组).使用结扎冠状动脉左前降支来构建AMI模型;造模成功后,SBP灌胃干预8周.通过小动物超声心动图检测各组大鼠的心功能;苏木精-伊红(HE)染色评估大鼠的心肌梗死面积;ELISA检测血清中促炎因子IL-6及TNF-α的表达;qRT-PCR检测心肌组织Ⅰ型和Ⅲ型胶原纤维转录水平表达;Masson染色分析心肌组织胶原蛋白表达情况;Western blotting检测心肌组织TGF-β1、p-Smad2/3及p-ERK1/2蛋白的表达水平.结果 与sham组比较,模型组大鼠出现明显心功能下降(P<0.01),心肌梗死面积增加(P<0.000 1),血清炎症因子TNF-α和IL-6表达增高(P<0.01),心肌组织Ⅰ型和Ⅲ型胶原纤维转录水平增高(P<0.001),胶原纤维含量明显增加(P<0.000 1),TGF-β1、p-Smad2/3及p-ERK1/2蛋白的表达增高(P<0.000 1).与模型组相比,L-SBP组和H-SBP组AMI大鼠心功能改善(P<0.05),心肌梗死面积缩小(P<0.001),炎性因子表达及心肌纤维化程度明显下降(P<0.05),TGF-β1、p-Smad2/3及p-ERK1/2蛋白的表达降低(P<0.05).与L-SBP组比较,H-SBP组心功能进一步改善(P<0.05),心肌梗死面积进一步缩小(P<0.01),炎性因子表达及心肌纤维化程度均下降(P<0.05),TGF-β1、p-Smad2/3及p-ERK1/2蛋白的表达降低(P<0.05).结论 SBP可通过抑制TGF-β/Smad/ERK信号通路抑制AMI大鼠全身炎症反应,进而逆转AMI大鼠心肌纤维化程度,促进受损心肌的修复,改善心功能.
Objective To explore the effect of Shexiang Baoxin pill(SBP)on myocardial fibrosis progression in rats with acute myo-cardial infarction(AMI)based on the TGF-β/Smad/ERK signaling pathway.Methods Forty-eight male SD rats were randomly di-vided into sham group,model group,low-dose SBP group(L-SBP),and high-dose SBP group(H-SBP).AMI model was induced by li-gation of the left anterior descending coronary artery.After successful modeling,the rats in L-SBP group and H-SBP group were admini-stered orally with SBP for 8 weeks.The cardiac functions of rats in each group were detected by small animal echocardiography.Hema-toxylin-eosin(HE)staining was used to evaluate the myocardial infarction area of rats.ELISA was used to detect the expressions of pro-inflammatory cytokines IL-6 and TNF-α in serum.qRT-PCR was used to measure the transcription levels of myocardial type Ⅰ and Ⅲcollagen fibers.Masson's trichrome staining was performed to analyze collagen fiber expression in myocardial tissue.Western blotting was used to detect the expressions of TGF-β1,p-Smad2/3,and p-ERK1/2 proteins in myocardial tissue.Results Compared with sham group,the heart function decreased(P<0.05),the myocardial infarct size increased(P<0.000 1),serum levels of TNF-α and IL-6 increased(P<0.01),the transcriptional levels of type Ⅰ and type Ⅲ collagen fibers in myocardial tissue increased(P<0.001),the contents of collagen fibers increased significantly(P<0.000 1),and the expressions of TGF-β1,p-Smad2/3,and p-ERK1/2 proteins increased in model group(P<0.05).Compared with model group,the heart function was improved in L-SBP group and H-SBP group(P<0.05),the myocardial infarct size decreased(P<0.001),the levels of inflammatory factors and the degree of myocardial fibrosis decreased significantly(P<0.05),and the expressions of TGF-β1,p-Smad2/3,and p-ERK1/2 proteins decreased(P<0.05).Com-pared with L-SBP group,the heart function was further improved(P<0.05),the myocardial infarct size further decreased(P<0.01),the levels of inflammatory factors and the myocardial fibrosis decreased(P<0.05),and the expressions of TGF-β1,p-Smad2/3,and p-ERK1/2 proteins decreased in H-SBP group(P<0.05).Conclusion SBP can inhibit the systemic inflammatory response in AMI rats by suppressing the TGF-β/Smad/ERK signaling pathway,thereby reversing myocardial fibrosis,promoting repair of damaged myo-cardium,and improving heart function.
刘茂林;樊林花;尚小森;卫兵艳
山西医科大学实验动物中心,实验动物与人类疾病动物模型山西省重点实验室,太原 030001||山西医科大学资产管理部实验科山西医科大学实验动物中心,实验动物与人类疾病动物模型山西省重点实验室,太原 030001太原市中心医院心内科山西医科大学实验动物中心,实验动物与人类疾病动物模型山西省重点实验室,太原 030001
医药卫生
麝香保心丸急性心肌梗死纤维化IL-6TNF-α心功能TGF-β/Smad/ERK信号通路
Shexiang Baoxin pillacute myocardial infarctionfibrosisIL-6TNF-αcardiac functionTGF-β/Smad/ERK signaling pathway
《山西医科大学学报》 2025 (6)
636-643,8
太原市科技计划项目(202264)山西省卫生健康委科研项目(2019122)山西省基础研究计划项目青年科学研究项目(202403021212288)
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