Study on mechanism of Suixin Decoction improving ventricular remodeling in heart failure rats through ROS-mediated activation of NLRP3 inflammasome
Objective:To observe the effect of Suixin Decoction on ROS-mediated NLRP3 inflammasome activation,to elucidate the molecular mechanism of f Suixin Decoction in improving ventricular remodeling in heart failure.Methods:SD rats were randomly divided into the sham-operation group,the model group,low-dose group,the middle-dose group,the high-dose group of Suixin Decoction,and the Western medicine group,except for the sham-operation group,the left anterior descending branch ligation method was used to construct a rat heart failure model,and the corresponding drug treatments were given respectively.Echocardiography was used to determine the level of cardiac function and ventricular remodeling indicators,ELISA was used to detect the content and activity of serum CK,CK-MB,LDH,SOD,MDA and GSH-Px in each group,HE and Masson staining were used to assess myocardial pathologic morphology and collagen deposition,and the level of apoptosis of cardiomyocytes was detected by Tunel staining.H9c2 cardiomyocytes were taken and divided into control group,model group,low-dose group,the middle-dose group,the high-dose group of Suixin Decoction and Western medicine group.Except for the control group,the cell model was constructed by hypoxia/re-oxidation(H/R)method and the corresponding serum was given for intervention.The morphology of cardiomyocytes was observed under microscopy,the apoptosis level of cardiomyocytes was detected by Tunel staining,the ROS level of cardiomyocytes was detected by flow cytometry,and the expression of NLRP3 inflammasome-associated proteins was detected by Western Blot,respectively.Results:Compared with the sham-operated group,the levels of LVEDd,LVESd,CK,CK-MB,LDH,GSH-Px and the activity of SOD in the model group of rats were significantly higher,and the myocardial pathology scores,collagen staining area and the number of Tunel-positively stained cells were significantly increased,while the levels of LVEF,LVFS and MDA were significantly reduced(P＜0.01).Compared with the model group,the levels of LVEDd,LVESd,CK,CK-MB,LDH,GSH-Px and the vigor of SOD in rats of the Suixin Decoction group were significantly reduced,the myocardial pathology scores,collagen staining area and the number of positively stained cells of Tunel were significantly reduced,and the levels of LVEF,LVFS and MDA were significantly increased(P＜0.05,P＜0.0l).In addition,compared with cells in the control group,the number of Tunel-positively stained cells and ROS levels in the model group were significantly increased,and the expression of NLRP3,Caspase-1 p20,Mature IL-1β,Pro IL-1β,Mature IL-18,Pro IL-18,and GSDMD-NT proteins were significantly up-regulated,and the expression of GSDMD-FL protein was significantly down-regulated(P＜0.01).Compared with the model group,the number of Tunel-positively stained cells and the level of ROS in the Suixin Decoction group were significantly reduced,the NLRP3,Caspase-1 p20,Mature IL-1 β,Pro IL-1β,Mature IL-18,Pro IL-18,and GSDMD-NT protein expression was significantly down-regulated,and GSDMD-FL protein expression was significantly up-regulated(P＜0.01).Conclusion:Suixin Decoction is able to inhibit NLRP3 inflammasome activation via ROS and improve ventricular remodeling,thus exerting a therapeutic effect on heart failure.
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