The Effect of Shenqi Jianxin Formula(参芪健心方)on Cardiomyocyte Pyroptosis in Chronic Heart Failure Model Rats Based on the NLRP3/Caspase-1 Signaling Pathway
Objective To investigate the possible mechanism of Shenqi Jianxin Formula(参芪健心方)in the treatment of chronic heart failure(CHF)from the perspective of pyroptosis.Methods Fifty-two rats were randomly divided into sham operation group(n=8)and modeling group(n=44).In the modeling group,the anterior descending branch of the left coronary artery was ligated to construct CHF rat model.Forty successfully-modelled rats were ran-domly divided into model group,Entresto group,Shenqi Jianxin Formula group,MCC950 group and the combination group(Shenqi Jianxin Formula plus MCC950),with 8 rats in each group.In Shenqi Jianxin Formula group,7.4 g/(kg·d)of Shenqi Jianxin Formula was given by gavage,while in Entresto group,68 mg/(kg·d)of Entresto suspen-sion was given by gavage;in MCC950 group,MCC950 was injected intraperitoneally with 10 mg/kg once every other day,and in the combination group,7.4 g/(kg·d)of Shenqi Jianxin Formula was given by gavage,and MCC950 was injected intraperitoneally with 10 mg/kg once every other day;10 ml/(kg·d)of saline was given by gavage in the sham operation group and the model group.After 3 weeks of continuous intervention,serum brain B-type natriuretic pep-tide(BNP),creatine kinase isoenzyme MB(CK-MB),interleukin 1β(IL-1β),and interleukin 18(IL-18)levels were detected by ELISA;HE staining and MASSON staining were used to observe pathological changes in rat myocar-dium.Except for the Entresto group,western blot technique was used to detect the expression of NOD-like receptor protein 3(NLRP3),caspase-1,and apoptosis-associated speck-like protein possessing a caspase-recruiting domain(ASC);RT-PCR was used to detect the expression of NLRP3 and caspase-1 mRNA.Results Compared with the sham operation group,HE staining of rats in the model group showed obvious myocardial injury,while MASSON staining showed increased area of collagen fibrosis,and serum BNP,CK-MB,IL-1β,IL-18,myocardial tissue NLRP3,caspase-1,ASC protein expression and NLRP3,caspase-1 mRNA expression were all elevated(P＜0.05).Compared with those in the model group,cardiomyocyte injury of rats and collagen fibrosis area were reduced,and serum BNP,CK-MB,IL-1β,and IL-18 contents were all reduced in Shenqi Jianxin Formula group,Entresto group,MCC950 group,and the combination group;except for Entresto group,myocardial tissue NLRP3,caspase-1,ASC protein expres-sion and NLRP3,caspase-1 mRNA expression were reduced in the remaining three medication group(P＜0.05).Compared with Shenqi Jianxin Formula group,the MCC950 group and the combination group showed decreased serum IL-1β and IL-18 content,collagen fibrosis area,myocardial tissue NLPR3,caspase-1 protein expression,and caspase-1 mRNA expression,and decreased ASC and NLRP3 mRNA expression was shown in the combination group(P＜0.05).Compared with MCC950 group,collagen fibrosis area was reduced,and serum IL-18 content,NLRP3,caspase-1 mRNA expression were reduced in the combination group(P＜0.05).Conclusion Shenqi Jianxin Formula can effectively improve the myocardial injury and heart failure in rats with CHF,and its mechanism may be related to the inhibition of cardiomyocyte pyroptosis through NLPR3/Caspase-1 pathway to reduce the level of intramyocardial inflam-mation.The combined use of MCC950 with Shenqi Jianxin Formula could more effectively inhibite myocardial pyrop-tosis,with better therapeutic result than single use of each part.
NETL
NSTL
万方数据
维普
