miR-1283/Atg5、Atg12对高血压病血瘀证血管内皮细胞自噬的调节作用及机制研究

Hypertension has become a serious public health problem and become important to control it.According to the evidence,blood stasis syndrome in TCM throughout the development of hypertension.However,the molecular mechanism of hypertension with blood stasis syndrome has not been elucidated yet.The applicant team found that in preliminary works,miR-1283 plays an important role in hypertension with blood stasis syndrome,think it may be related to the regulate of endothelial autophagy. According to target prediction,we find Atg5,Atg12 is a key target genes of miR-1283.So,we put forward a scientific hypothesis that miR-1283 may be mediated Atg5,Atg12 to regulate endothelial autophagy and participate in the formation process of hypertension with blood stasis syndrome.Based on the previous research, with the combination of in vitro and in vivo experiment method,this project will clear the effect of miR-1283 in hypertension with blood stasis syndrome at first, then clear the targeting relations of miR-1283 and Atg5,Atg12.After that, find whether miR-1283 can mediate Atg5,Atg12 to regulate vascular endothelial cell autophagy process and participate in formation of hypertension with blood stasis syndrome.Finally,use Taohuasiwutang on the corresponding verification,provide scientific basis for prevention and control of hypertension with blood stasis syndrome.

高血压病已成为严重的公共卫生问题，控制其发生发展是亟待解决的重要课题。诸多证据表明，中医血瘀证贯穿于高血压病的发生发展过程。然而，对于高血压病血瘀证的分子机制迄今尚未阐明。申请者所在团队前期研究发现：miR-1283在高血压病血瘀证中起重要作用，可能与调节血管内皮自噬有关。靶基因预测发现Atg5、Atg12是miR-1283的关键靶基因。据此，提出科学假说：miR-1283可能介导Atg5、Atg12调节血管内皮自噬，以参与高血压病血瘀证的形成过程。本项目拟在前期研究基础上，利用体内结合体外的实验方法，首先明确miR-1283在高血压病血瘀证形成中的作用；然后，明确miR-1283与Atg5、Atg12的靶向关系；接着，探讨miR-1283是否介导Atg5、Atg12调节血管内皮细胞自噬过程，以参与高血压病血瘀证形成；最后，应用桃红四物汤进行方证相应验证，为防治高血压病血瘀证提供科学依据。

本项目研究发现miR-1283在高血压病血瘀证中起重要作用，其作用机制与miR-1283调节血管内皮自噬有关。靶标验证发现Atg5是miR-1283的关键靶基因。体外细胞实验发现，miR-1283可介导Atg5、Atg12调节血管内皮自噬，以参与高血压病血瘀证的形成过程。体内动物实验研究发现，miR-1283对高血压病大鼠产生作用。此研究项目探讨了miR-1283在高血压病血瘀证的作用及机制。