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基于TGF-β-Smads信号的氧化苦参碱干预急性心肌梗死诱发实验性大鼠心肌纤维化的研究 被引量:34

Protective effect of TGF-β-Smads signal-based oxymatrine on myocardial fibrosis induced by acute myocardial infarction in rats
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摘要 目的:研究氧化苦参碱(OMT)对大鼠急性心肌梗死诱发实验性心肌纤维化的保护作用及对TGF-β-Smads信号通路的影响。方法:采用冠状动脉结扎术复制大鼠急性心肌梗死模型,随机分为模型组、OMT高、中、低剂量组(50,25,12.5mg.kg-1)、卡托普利组(50 mg.kg-1);假手术组(Sham)只做冠状动脉穿线而不结扎。模型复制8周后采用HE与Masson染色分析心肌纤维化病变程度,半定量RT-PCR分析TGF-β-Smads信号系统mRNA的表达。结果:模型组急性心肌梗死8周后,病理组织学检查提示心肌细胞减少,细胞外基质沉积,胶原含量增加;RT-PCR结果提示TGF-β1,TβR1,Smad2,Smad3,Smad4 mRNA表达明显增加,而Smad7 mRNA的表达显著降低,与Sham组比较,差异显著。OMT显著抑制急性心肌梗死8周后诱发的实验性心肌纤维化,抑制TGF-β1,TβR1,Smad2,Smad3,Smad4 mRNA表达的上调和增加Smad7 mRNA的表达。结论:OMT对急性心肌梗死诱发实验性心肌纤维化具有一定的抑制作用,其作用机制与TGF-β-Smads信号系统密切相关。 Objective: To study the protective effect of oxymatrine(OMT) on myocardial fibrosis induced by acute myocardial infarction in rats and its effect on TGF-β-Smads signal pathway.Method: Arteria coronaria ligation-induced acute myocardial infarction model was established in rats.The survived rats were randomly allotted into the model group,50,25,12.5 mg·kg-1 OMT groups,the 50 mg·kg-1 captopril group,and the Sham-operated group which was treated as the model group without the arteria coranaria ligation.After 8 weeks of ligation,myocardial fibrosis was detected by HE and Masson staining,and the RT-PCR method were used to detect the expression of mRNA of TGF-β-Smads signal system.Result: The histopathological examination showed decrease in cardiocytes,deposition of extra-cellular matrix,and increase of collagen contents after 8 weeks of ligation.RT-PCR results showed that mRNA expressions of TGF-β1,TβR1,Smad2,Smad3 and Smad4 significantly increased,but mRNA expression of Smad7 is remarkable lower than the sham-operated group.Treatment with OMT for 8 weeks could remarkably inhibit myocardial fibrosis,decrease mRNA expressions of TGF-β1,TβR1,Smad2,Smad3,and Smad4,and increase mRNA expressions of Smad7.Conclusion: OMT has the inhibitory effect on the experimental myocardial fibrosis induced by AMI in rats.Its mechanism may be closely related to TGF-β-Smads signal system.
出处 《中国中药杂志》 CAS CSCD 北大核心 2012年第5期632-636,共5页 China Journal of Chinese Materia Medica
基金 国家自然科学基金项目(30701024 81173586) 贵州省科技攻关项目(黔科合[2007]1035号) 贵州省国际科技合作基金(黔科合外G字[2009]700115号)
关键词 氧化苦参碱 心肌纤维化 TGF-β-Smads oxymatrine myocardial fibrosis TGF-β-Smads
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