VDAD1 Mediates The Mechanism Of Puerarin Protecting H9c2 From Hypoxia-reoxygenation Ferroptosis And Apoptosis

Objective: Puerarin(Pue)is a natural isoflavone traditional Chinese medicine commonly used clinically for cardiovascular protection,and it has a protective effect in cardiac ischemia-reperfusion injury(IRI).This paper aims to study the protective effect and possibleMethod:1.The drug toxicity of different concentrations of Pue(0,2.5,5,10,20,40 and 80μM)on H9c2 was detected by CCK-8,and the A/R injury model was established after48 hours of Pue pretreatment.2.According to the treatment method,H9c2 cardiomyocyte-like cells were divided into four groups: control group,A/R group,Pue/ferroptosis inhibitor(Fer-1,5μM)pretreatment A/R injury group,Fer-1 was advanced 2h For pretreatment,cell viability was detected by CCK-8 and LDH,and ferroptosis indicators were detected in terms of MAD,ROS,GSH/GSSG,iron ion quantification,and the expression of m RNA and protein levels of GPX4 and PTGS2.3.Molecular docking predicts the possibility of binding between Pue and VDAC1.The p AD-VDAC1 overexpression virus was transfected with Pue pretreatment and A/R treatment was performed,and the empty virus group was used as a control to detect cell viability,ferroptosis-related indicators,and mitochondrial membrane channels and other related functions.Result:1.Appropriate concentration of Pue has no obvious effect on the viability of normal H9 c cells,and can protect H9c2 from damage during A/R.2.A/R treatment can lead to ferroptosis in H9c2 cardiomyocytes,while Pue pretreatment can protect ferroptosis.3.There is a suitable combination possibility between VDAC1 and Pue.4.Pue alleviates A/R-induced cardiomyocyte ferroptosis by inhibiting VDAC1.5.Pue regulates mitochondrial membrane potential and mitochondrial membrane permeability transition pore activity by inhibiting VDAC1,and promotes apoptosis.Conclusion:1.Pue pretreatment can effectively reduce the injury of H9c2 cardiomyocytes in the A/R injury model.2.Pue can reduce ferroptosis and cell apoptosis caused by VDAC1-mediated hypoxia-reoxygenation injury.