Guanxinning tablet ameliorates cardiomyocyte pyroptosis in rats with dilated cardiomyopathy by inhibiting the NLRP3/ASC/Caspase-1 pathway
10.3969/j.issn.1005-4847.2024.03.007
- VernacularTitle:冠心宁片抑制NLRP3/ASC/Caspase-1通路改善阿霉素诱导的扩张型心肌病大鼠心肌细胞焦亡
- Author:
Jiajun SHI
1
;
Qinqin YANG
;
Danting FU
;
Chunwei ZHENG
;
Yan ZHANG
;
Yu CHEN
Author Information
1. 浙江省中医药研究院实验动物中心,杭州 310007
- Keywords:
Guanxinning tablet;
dilated cardiomyopathy;
cardiomyocyte pyroptosis;
NLRP3;
Caspase-1
- From:
Acta Laboratorium Animalis Scientia Sinica
2024;32(3):337-346
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protective effect of Guanxinning(GXN)tablet on dilated cardiomyopathy(DCM),and to explore its effect and mechanism in pyroptosis of cardiomyocytes via the NLRP3/ASC/Caspase-1 pathway.Methods Rats were divided into GXN low-dose,GXN high-dose,digoxin,model control,and normal control groups.The DCM model was induced by multiple intraperitoneal injections of 17.5 mg/kg doxorubicin(DOX).The drug was administered at the same time as the model was established for 10 weeks.After the last administration,echocardiography was used to assess cardiac function indexes.After sacrificing the rats,serum was collected to measure IL-1β and IL-18 levels.RT-PCR was used to detect mRNA expression of NLRP3,ASC,Caspase-1,NF-κB,TXNIP,IL-1β,and IL-18.Immunohistochemistry and immunofluorescence staining and Western Blot were used to assess NLRP3,ASC,Caspase-1,IL-1β,and IL-18,GSDMD and GSDMD-NT protein,and TUNEL staining result.Changes in the microstructure of cardiomyocytes were observed by transmission electron microscopy.Results Compared with the normal control group,IVSs,IVSd,LVPWs,FS,SV,EF,and HR of the model control group were significantly reduced,LVIDs,ESV,and serum IL-1β and IL-18 were significantly increased,NLRP3,ASC,Caspase-1,NF-κB,TXNIP,IL-1β and IL-18 mRNA expression was significantly increased,and NLRP3,ASC,Caspase-1,IL-1β,IL-18 and GSDMD-NT protein expression and the TUNEL staining area were increased significantly,and the microstructure of cardiomyocytes changed significantly.Compared with the model control group,GXN significantly increased IVSs,SV,FS,EF,and HR,significantly reduced LVIDs,ESV,and the serum levels of IL-1β and IL-18,and reduced NLRP3,ASC,Caspase-1,NF-κB,TXNIP,IL-1β,and IL-18 mRNA expression,NLRP3,ASC,Caspase-1,IL-1β,IL-18 and GSDMD-NT protein expression,and the TUNEL staining area.Additionally,the microstructure was improved significantly.Conclusions GXN alleviates cardiomyocyte pyroptosis in rats with DCM by inhibiting the NLRP3/ASC/Caspase-1 pathway.
