葛根素通过MCP-1和TGF-β途径抑制小鼠心肌梗死后心肌过度纤维化

发布时间：2018-01-10 04:23

本文关键词：葛根素通过MCP-1和TGF-β途径抑制小鼠心肌梗死后心肌过度纤维化　出处：《南京医科大学》2017年博士论文　论文类型：学位论文

【摘要】：TGF-β和炎症反应在心肌梗死后心肌纤维化过程中起到了重要的作用。葛根在中国传统医学中应用已千年,葛根素是从葛根中提取的具有治疗价值的活性成分。目前葛根素多应用于治疗糖尿病及心脑血管疾病。最近一些研究发现通过主动脉缩窄及异丙肾上腺素刺激后形成心肌纤维化,葛根素具有抑制其心肌过度纤维化,但针对心肌梗死后纤维化的研究较少。故本研究的目的是明确葛根素是否具有抑制心肌梗死后纤维化程度,并对其机制进行进一步探讨。通过结扎C57/B6小鼠前降支建立心肌梗死模型,通过马松染色,检测胶原Ⅰ和3、α-SMA,来明确纤维化程度。通过免疫组化方法、酶联免疫吸附法及实时定量PCR方法,检测心肌梗死组及心肌梗死后应用葛根素组的F4/80、MCP-1、TGF-β的表达水平。TGF-β下游的SMAD2/3的表达则通过westernblot方法来检测。最终结果表明葛根素可以抑制单核巨噬细胞的聚集和激活,减轻TGF-β在心肌组织中表达,从而最终减轻心肌梗死后心肌纤维化程度。我们的结果更进一步显示了 MCP-1和TGF-β两者在心肌梗死后有紧密的联系。因此,本研究表明葛根素对心梗后纤维化抑制作用的机制可能与抑制MCP-1的表达和TGF-β/SMAD通路有关,同时也揭示葛根素可以成为减轻心肌梗死后心肌纤维化的很有前景的药物。
[Abstract]:TGF- 尾 and inflammation play an important role in myocardial fibrosis after myocardial infarction. Pueraria lobata has been used in traditional Chinese medicine for thousands of years. Puerarin is a therapeutic active component extracted from Pueraria lobata. At present, puerarin is widely used in the treatment of diabetes mellitus and cardiovascular and cerebrovascular diseases. Recent studies have found that puerarin is stimulated by aortic constriction and isoproterenol. To form myocardial fibrosis. Puerarin can inhibit the excessive fibrosis of myocardium, but there are few studies on the fibrosis after myocardial infarction. Therefore, the purpose of this study is to determine whether puerarin has the ability to inhibit the degree of fibrosis after myocardial infarction. The myocardial infarction model was established by ligating the anterior descending branch of C57 / B6 mice, and collagen I and 3, 伪 -SMA were detected by Ma Song staining. By immunohistochemical method, enzyme-linked immunosorbent assay (Elisa) and real-time quantitative PCR method, the F4 / 80 MCP-1 was detected in myocardial infarction group and puerarin group after myocardial infarction. The expression level of TGF- 尾. The expression of SMAD2/3 downstream of TGF- 尾 was detected by westernblot. The final results showed that puerarin could inhibit the aggregation of mononuclear macrophages. Set and activate. The expression of TGF- 尾 in myocardium was reduced. Our results further show that MCP-1 and TGF- 尾 are closely related after myocardial infarction. The present study suggests that the inhibitory mechanism of puerarin on post-myocardial fibrosis may be related to the inhibition of MCP-1 expression and TGF- 尾 / SMAD pathway. It also revealed that puerarin may be a promising drug to alleviate myocardial fibrosis after myocardial infarction.
【学位授予单位】：南京医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R542.22

【参考文献】