Abstract: OBJECTIVE: To investigate relationships between expression in the succinate receptor pathway and cardiomyocyte injury under a hypoxic environment. METHODS: Primary cardiomyocytes of suckling mice were cultured in vitro under different hypoxic environment. The siRNA interference technology was used to reduce expression of intracellular succinate receptor G protein-coupled receptor 91 (GPR91). The different cultures were randomly divided into the control (CTL),CTL+siGPR91 group,succinate group,succinate+siGPR91 group,hypoxic CTL group,hypoxic CTL+siGPR91 group,hypoxic succinate group and hypoxic Succinate+siGPR91 group. After 5 days of cultivation under 10% oxygen content,CCK-8 was used to detect the survival rate of cardiomyocytes. In addition,cellular ATP contents of primary cardiomyocyte hypoxia model were determined. Changes in expression of Akt and P-Akt in the PI3K/Akt protein pathway were determined using the Western blot. RESULTS: Compared with the CTL group,the survival rate and the content of ATP of myocardial cells were reduced,and expressions of BNP and CaMK Ⅱ were up-regulated in the hypoxic environment (P < 0.05). Compared with the CTL group,expression levels of GPR91 in the siRNA interference group were suppressed (P < 0.05). At the same time,myocardial cell survival rates and ATP contents were increased, BNP and CaMK Ⅱ protein expressions were down-regulated,and phosphorylation levels of PI3K and levels of downstream signaling molecule Akt were reduced (P < 0.05). CONCLUSION: Our data show that GPR91 was involved in the pathological process of myocardial ischemic injury by regulating the phosphorylation of PI3K/Akt pathway.

Key words: primary cardiomyocyte, myocardial hypoxia, GPR91, PI3K/Akt pathway