The Study Of Preventive Effect And Mechanism Of Resveratrol On Monocrotaline-induced Pulmonary Arterial Hypertension Rats

ObjectivePulmonary hypertension is a progressive increase in pulmonary vascular resistance and pulmonary artery pressure that eventually leads to increased right ventricular load and right ventricular dysfunction.Resveratrol(RES)is a polyphenolic compound extracted from various plants,with a variety of pharmacological effects such as anti-inflammatory,anti-oxidation,anti-platelet aggregation.This study aimed to investigate whether resveratrol can protect against pulmonary hypertension by inhibiting the NLRP3/caspase-1/IL-1? inflammatory signaling pathway in monocrotaline-induced pulmonary hypertension in rats.Methods48 male Sprague-Dawley rats were randomly and equally divided into 4 groups:(1)for control group,on day 1,1%DMSO was injected intraperitoneally(i.p.)30min before injecting(i.p.)a single dose of normal saline;then treated normal saline(by gavage)from day 21 to day 42.(2)for monocrotaline-induced(MCT)group,on day 1,1%DMSO was injected(i.p.)30min before MCT-induced PAH;then treated normal saline(by gavage)from day 21 to day 42.(3)for RES group,1%DMSO was injected(i.p.)30min before MCT-induced PAH;then treated RES(60mg/Kg,by gavage)from day 21 to day 42.(4)for AC-YVAD-CMK(3mg/kg,i.p.),the caspase-1 inhibitor(YVAD)group,was injected before MCT-induced PAH;then treated normal saline(by gavage)from day 21 to day 42.On day 43,hemodynamic changes,right ventricular hypertrophy,and lung morphological features were examined.Expression of NLRP3,caspase-1 and IL-1? in lung were assessed using Western blot analysis and Immunohistochemistry.SOD and MDA level in serum were measured as index of oxidative stress.ResultsCompared with MCT group,RES reduced the right ventricle systolic pressure,the right ventricular hypertrophy index and the wall thickness/external diameter ratio of pulmonary arteries.RES also downregulated the expression of NLRP3,caspase-1 and IL-1?;And elevated levels of oxidative stress.ConclusionRES alleviated MCT-induced PAH through regulation of NLRP3/caspase-1/IL-1? signal pathway in rats.