Telmisartan inhibits NLRP3/GSDMD/Caspase-1 signaling pathway to improve cardiac function in chronic heart failure rats
Objective To explore the potential mechanism of telmisartan in improving chronic heart failure based on NOD-like receptor thermal protein domain associated protein 3(NLRP3)/Gasdermin D(GSDMD)/Caspase-1 signaling pathway.Methods 40 rats were randomly divided into control group,model group,Telmisartan(30 mg/kg)and MCC950(NLRP3 inhibitor,10 mg/kg)group.Chronic heart failure rat model was established by subcutaneous injection of isoproterenol.The heart function of rats was measured by ultrasound.The pathological changes of myocardial tissue were detected by HE staining,and the collagen fiber deposition was detected by Masson staining.The ultrastructure of myocardial tissue was observed by transmission electron microscopy.The levels of interleukin-1 β(IL-1β)and IL-18 in serum were detected by enzyme-linked immunosorbent assay(ELISA).The expressions of NLRP3,GSDMD,apoptosis-related spot-like protein(ASC),pro-caspase-1 and Cleaved-caspase-1 were detected by Western blot.Results Telmisartan significantly improved cardiac function,ameliorated pathological injury,inhibited myocardial fibrosis,significantly decreased the levels of IL-1β and IL-18 in serum of rats,and significantly inhibited the expressions of NLRP3,GSDMD,ASC,pro-caspase-1 and Cleaved caspase-1 in myocardial tissue of rats.Conclusion Telmisartan can improve cardiac function in rats with chronic heart failure by inhibiting the NLRP3/GSDMD/Caspase-1 signaling pathway.
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