Relationship between SR9009 and NLRP3 in septic myocardial injury
Objective:To evaluate the relationship between Rev-erbα agonist SR9009 and NLRP3 inflam-masome in lipopolysaccharide(LPS)-induced septic myocardial injury mice.Methods:A total of thirty-two healthy male C57BL/6 mice were intraperitoneally injected with LPS(15 mg/kg)to establish the myocardial injury model of sepsis.They were randomly divided into the control group(control group),sepsis group(LPS group),SR9009 group(SR group),and sepsis+SR9009 group(LPS+SR group),with eight rats in each group.In the LPS+SR group,SR9009 was intraperitoneally adminis-tered at 50 mg/kg 18 hours before LPS injection,and the mice in the SR9009 group were intraperito-neally injected with SR9009 at 50 mg/kg at the same time without LPS injection.Echocardiography was used to detect cardiac function,and HE staining was used to detect the degree of cardiac tissue damage.The contents of troponin(cTnⅠ),creatine kinase isoenzyme(CK-MB),and lactate dehydro-genase(LDH)in serum were detected by ELISA.Western Blot was used to detect the relative pro-tein expressions of NLRP3,IL-1β,and IL-18.Results:Compared with those in the control group,no significant changes were found in the SR group,while in the LPS group,the left ventricular wall thickness and left ventricular ejection fraction were significantly decreased,left ventricular end-systolic volume was significantly increased,the serum levels of myocardial enzymes cTnⅠ,CK-MB,and LDH were also significantly increased,the expression of NLRP3,IL-1β,and IL-18 in myocardial tis-sue was up-regulated(P＜0.05),and significant pathological changes of myocardial tissue were found.Compared with the changes in the LPS group,the LPS+SR group showed significantly in-creased left ventricular wall thickness and left ventricular ejection fraction,decreased left ventricular end-systolic volume,and decreased serum levels of cTnⅠ,CK-MB,and LDH.The expression of in-flammasome NLRP3 and proinflammatory cytokines IL-1β and IL-18 was also down-regulated(P＜0.05),and pathological damage of myocardial tissue was alleviated after SR9009 treatment.Conclusion:SR9009 plays a protective role in sepsis-induced myocardial injury in mice by inhibiting NLRP3,IL-1β,and IL-18.
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