Study On The Mechanism Of Intermittent Hypoxia Induced Myocardial Injury In Rats Based On MR-1

Objective: Patients with obstructive sleep apnea hypopnea syndrome(OSAHS)often have cardiac insufficiency mainly due to hypoxia/reperfusion injury caused by chronic intermittent hypoxia(CIH).Inflammation and oxidative stress are involved in the cardiovascular events of OSAHS patients.Studies have found that myofibrillation regulator-1(MR-1)participates in the pathological process of OSAHS-induced myocardial injury,but the specific mechanism is still unclear.Methods: We used a CIH-induced rat model to simulate the process of OSAHS disease.Indices of myocardial injury,inflammation,and oxidative stress were detected using quantitative PCR and enzyme-linked immunosorbent assay(ELISA).After administration of adeno-associated viral vector(AAV)encoding silencing RNA against MR-1,we examined expression of the classic antioxidant stress pathway protein NF-E2-related factor 2(Nrf2)using western blotting.Results: We found that HW/BW,BNP,ANP and Ang II increased in the CIH+saline group.And then we found that levels of serum inflammatory factors tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,and IL-8 were increased,and we further observed disturbance of the oxidative stress system,in which the content of reactive oxygen species(ROS),superoxide dismutase(SOD),reduced glutathione(GSH),and malondialdehyde(MDA)was enhanced in CIH-induced rats.Subsequently,we detected that expression of Nrf2 and heme oxygenase-1(HO-1)was slightly increased,while the expression of Kelch-like ECH-associated protein 1(Keap-1)was significantly increased in the CIH model.Interestingly,after administration of silencing MR-1 AAV,high expression of HW/BW,BNP,ANP and Ang II is reduced,the elevated levels of inflammatory factors were reduced,and the disordered oxidative stress system was corrected.Additionally,the expression of Nrf2 and HO-1 was distinctly increased,but the high expression of Keap-1 was decreased.Conclusion: Our research results demonstrate that silencing MR-1 rescued the myocardium the injury from inflammatory and oxidative stress in CIH-induced rats by administration of the Nrf2 signaling pathway.