从m6A甲基化MALAT1调控自噬研究丹参通络解毒汤促心肌缺血再灌注损伤血管新生的作用及机制

心肌缺血再灌注损伤（IRI）是亟待解决的问题，m6A甲基化修饰lncRNA在IRI中起关键作用，但机制未明。前期研究发现丹参通络解毒汤对冠心病疗效显著，其通过抑制MALAT1表达，调节自噬稳态，促进血管新生，保护心肌IRI。为进一步探讨其作用机制，推测该方促心肌IRI血管新生的分子机制，可能与其通过m6A修饰的MALAT1竞争结合miR-126靶向CLCX12，抑制内皮细胞自噬有关。为验证推测，项目在动物和细胞水平上复制IRI模型，采用MeRIP-qPCR、GFP-LC3B融合蛋白示踪、双荧光素酶报告基因等技术，构建MALAT1、miR-126及METTL3等敲降或过表达载体，以m6A修饰MALAT1为切入点，从体内外研究其血管新生作用及分子机制，并观察该方对该过程影响，以期揭示心肌IRI发病新机制和干预靶点，阐明该方抗心肌IRI的确切机制，为防治心肌IRI新药研发提供科学依据。

Myocardial ischemia-reperfusion injury (IRI) is an urgent problem to be solved. m6A methylated lncRNA plays a key role in IRI, with unclear mechanism. Previous studies have found out that danshen tongluo detoxication decoction is effective in the treatment of coronary heart disease, regulating autophagy homeostasis, promoting angiogenesis and protecting myocardial IRI by inhibiting MALAT1 expression. In the process of the exploration of its mechanism of action, it is speculated that the molecular mechanism of promoting angiogenesis of myocardial IRI of this recipe may be related to the inhibition of autophagy of endothelial cells by the competitive binding of miR-126 to CLCX12 through m6A modified MALAT1.To verify the hypothesis, the IRI model was replicated at animal and cell levels, adopting MeRIP qPCR, GFP fusion LC3B protein tracer, dual luciferase report gene technology, such as building MALAT1, miR-126 and METTL3 to knock down or overexpression vector.The effects of m6A modified MALAT1 on angiogenesis and its molecular mechanism were studied in vitro and in Vivo,and observing the influence of this recipe on the process.In order to reveal the new pathogenesis and intervention target of myocardial IRI, clarify the exact mechanism of the prescription against myocardial IRI, and provide scientific basis for the research and development of new drugs for the prevention and treatment of myocardial IRI.