基于NLRP3炎症小体研究C1q/肿瘤坏死因子相关蛋白6对病毒性心肌炎细胞损伤的保护作用

doi:10.3969/j.issn.1006-6233.2023.02.07

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Abstract Objective: To investigate the role of C1q/tumor necrosis factor-related protein 6 (CTRP6) in mediating viral myocarditis-associated cardiac cell injury induced by Coxsackie B3 virus (CVB3) and explore the potential underlying mechanism. Methods: Human cardiac cell line AC-16 was applied to establish an in vitro model of viral myocarditis by infecting CVB3. CTRP6 overexpression was achieved by transfecting the CTRP6 expression vector. Cells were divided into four groups including the normal group, CVB3 infection group, CVB3 + empty vector group, and CVB3 + CTRP6 vector group. The mRNA expression was measured by real-time quantitative PCR (RT-qPCR). The protein expression was measured by Western blotting. The levels of creatine kinase-MB (CK-MB) and cardiac troponin-I (cTn-I) were assessed by corresponding kits. Cell apoptosis was measured by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. The concentrations of inflammatory cytokines were quantified by enzyme-linked immunosorbent assay (ELISA). Knockdown of AdipoR1 was achieved by RNAi silencing. Results: As compared with the normal group, infection of CVB3 significantly decreased the expression of CTRP6 in cardiac cells (P<0.01). Infection of CVB3 markedly increased the levels of CK-MB and cTn-I, and significantly enhanced the apoptosis and inflammatory cytokine release in cardiac cells (P<0.01). As compared with the CVB3 + empty vector group, overexpression of CTRP6 significantly downregulated the levels of CK-MB and cTn-I and attenuated the apoptosis and inflammatory cytokine release in cardiac cells infected with CVB3 (P<0.01). Overexpression of CTRP6 also inhibited the activation of NLRP3 inflammasome in CVB3-infected cardiac cells compared with the CVB3 + empty vector group (P<0.01). Silencing of AdipoR1 markedly abolished CTRP6-mediated protective effects on CBV3-induced cardiac cell injury (P<0.01). Conclusion: CTRP6 ameliorates viral myocarditis-associated cardiac cell injury induced by CBV3 through inhibition of NLRP3 inflammasome activation via the action on the receptor AdipoR1.

Key words： CTRP6 Viral myocarditis Coxsackie B3 NLRP3 inflammasome

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2023.02.07 OR http://www.hbyxzzs.cn/EN/Y2023/V29/I2/214

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