微小RNA-122(miR-122)参与高血压发病。Apelin(APLN)是miR-122的潜在靶基因之一，可调控血压与AMPK自噬信号。我们前一国家自然科学基金(No.91339108)研究发现，高血压血管损伤状态下miR-122和凋亡水平增加，伴血管外膜APLN表达下调，但miR-122对自噬信号与血管重构的调控作用尚不清楚。本课题拟利用miR-122、APLN基因敲除模型、自发性高血压大鼠、TAC术及经Ang II制备高血压血管损伤动物及血管外膜成纤维细胞模型，开展pAAV-miR-122、miR-122抑制剂和Apelin-13体内外干预实验，系统探讨miR-122与APLN对血管外膜自噬信号(AMPK/mTOR、Akt/Bcl2/Beclin-1、p62/LC3 II)、炎症小体及血管结构功能的影响，为确立miR-122与APLN作为高血压血管损伤早期防治新靶点提供科学依据。

MicroRNA-122 (miR-122) is involved in the onset of hypertension. Apelin (APLN) is one of the potential target genes of miR-122, which may modulate blood pressures and promote the expression of AMPK and its related autophagy signaling. In our former National Natural Science Foundation (No.91339108) study, we found that there were marked increases in levels of miR-122 and cellular apoptosis and a decrease in adventitial APLN expression in hypertension animal model with vascular injury. However, the regulatory roles of miR-122 in autophagy signaling and vascular remodeling remain unclear. This project intends to carry out in vitro and in vivo intervention experiments with pAAV-miR-122, miR-122 antagomiR and Apelin-13 by the use of the APLN gene knockout (KO) and miR-122KO model, spontaneously hypertensive rats and hypertensive vascular injury animal induced by an osmotic minipump with angiotensin II or by transverse aortic constriction (TAC) operation as well as cellular model of primary rat adventitial fibroblasts, and to implore effects of miR-122 and APLN on the vascular adventitial autophagy signal (AMPK/mTOR, Akt/Bcl2/Beclin-1, p62/LC3 II), inflammasome and the vascular function and structural changes. Therefore, this work will provide a scentific basis to establish miR-122 and APLN as new targets for early prevention and treatment of vascular injury in hypertension.