关键词: Vps16, 心肌缺血/再灌注, 自噬, 紫外线辐射抗性相关基因蛋白(UVRAG), Ras相关蛋白7(Rab7)

Abstract: Objective To investigate the role of vacuolar sorting protein 16 (Vps16) in myocardial ischemia-reperfusion (MI/R) injury in rats. Methods The rats were randomly divided into sham group, MI/R group, lentivirus blank vector (Lv-NC) group and lentivirus overexpressing Vps16 (Lv-Vps16) group, with 6 rats in each group. Left ventricular function was measured by echocardiography, including LVIDd and LVISd. LVFS and LVEF were calculated. ELISA was used to detect the levels of serum myocardial injury markers (CK-MB, cTnⅠ and LDH) and inflammatory factors (IL-6, TNF-α, and IL-1β). HE and TUNEL staining were employed to assess myocardial injury and apoptosis, while immunohistochemistry (IHC) and Western blot were used to determine the expression levels of Vps16, UV radiation-associated gene protein (UVRAG), Ras-associated protein 7 (Rab7), and autophagy- related proteins. Results Compared with the sham group, LVIDd, LVISd, CK-MB, cTnⅠ and LDH, the rate of TUNEL-positive cells and the levels of IL-6, TNF-α, IL-1β and p62 in the MI/R group were increased. LVFS, LVEF, Vps16, LC3Ⅱ/LC3Ⅰ, UVRAG, and Rab7 proteins were down-regulated (all P＜0.05). The myocardial tissue structure of MI/R group was disordered, indicating that the MI/R model was successfully constructed. Over-expression of Vps16 alleviated myocardial injury and inflammatory response, and improved cardiac function in rats. Conclusions Vps16 can alleviate MI/R injury by activating the UVRAG/Rab7 signaling to induce cardiomyocyte autophagy.

Key words: Vps16, myocardial ischemia-reperfusion, autophagy, UV radiation resistance associated gene protein(UVRAG), Ras-associated protein 7(Rab7)