Exploration of the effects and mechanism of paeoniflorin on the acute radiation-induced heart disease in male rats based on NLRP3/Caspase-1/GSDMD signaling pathway
Objective To explore the effects and mechanism of paeoniflorin(PF)on the acute radiation-in-duced heart disease(RIHD)in male rats based on the NLRP3/Caspase-1/GSDMD signaling pathway.Methods Male Wistar rats were randomly divided into 5 groups:blank control group(Con group),pure irradiation of 20 Gy group(Mod group),PF low dose+20 Gy irradiation group(L group),PF medium dose+20 Gy irradiation group(M group),PF high dose+20 Gy irradiation group(H group).A myocardial injury model was made by single 20 Gy precordial irradiation with 6 MVX ray.The PF groups were gavaged with PF low-dose(25.0 mg/kg),medium-dose(50.0 mg/kg)and high-dose(75.0 mg/kg)on every other day starting from 7 d before irradiation to 7 d after irradiation,while saline was gavaged in the Con group and the Mod group.ELISA was performed to detect the lev-els of IL-1 β and 1L-18 in serum.HE staining was adopted to observe the pathological damage of myocardial tis-sue.WB and IHC were used to detect the expressions of NLRP3,GAPDH,caspase-1,GSDMD and IL-1 β protein in myocardial tissue.Results Compared with the Con group,the expression levels of IL-1 β and IL-18 in serum were significantly higher in the Mod group(P＜0.05).Compared with the Mod group,the expression levels of IL-1βand IL-18 in serum were reduced in the PF groups.Compared with the Con group,the cardiomyocytes in the Mod group were extensively necrotic in large sheets,broken and disordered in arrangement,with a large number of in-flammatory cells infiltrating the myocardial interstitium and the disappearance of transverse myocardium.Com-pared with the Mod group,as the PF dose increased,the cells gradually returned to normal and arranged neatly.Be-sides,the infiltration of myocarditis cells decreased.Compared with the Con group,the expression levels of NL-RP3,Caspase-1,GSDMD and IL-1 β in myocardial tissue were significantly higher in the Mod group with signifi-cant difference(P＜0.05).Compared with the Mod group,the expressions of NLRP3,Caspase-1,GSDMD and IL-1βin myocardial tissue of the PF group decreased with the increase of PF dose.Conclusion Paeoniflorin can reduce myocardial inflammation and myocardial cell death caused by radiation-induced myocardial injury,thereby pro-tecting the myocardium.NLRP3 inflammasome can serve as a potential therapeutic target for radiation-induced myocardial injury.
万方数据
维普
