姜黄素预处理缓解小鼠脓毒症心肌病的作用和机制研究

Study of the effect of curcumin pretreatment on septic cardiomyopathy and mechanisms in mice

目的探究姜黄素(Cur)预处理对脓毒症小鼠心肌损害的保护作用以及SIRT1信号通路是否介导Cur心肌保护作用。方法通过小鼠盲肠结扎穿孔法(CLP)建立脓毒症模型。术前3 d每日给予Cur(100 mg/kg,灌胃)和SIRT1特异性抑制剂Sirtinol(5 mg/kg,腹腔注射)。CLP 48 h后,通过Millar导管技术检测小鼠心脏收缩与舒张功能,通过试剂盒检测丙二醛含量、超氧化物歧化酶和谷胱甘肽过氧化物酶活性,通过TUNEL染色检测心肌凋亡率,通过Western Blotting检测SIRT1信号通路和凋亡相关蛋白的表达情况。结果与Sham组相比,CLP后小鼠心脏收缩与舒张功能均明显受损,心肌组织丙二醛含量增加,而超氧化物歧化酶和谷胱甘肽过氧化物酶活性明显降低,凋亡率和Bax、Caspase 3表达量显著增加,Bcl-2的表达量明显降低(P <0.05)。Cur预处理可以明显改善心脏功能,抑制心肌氧化应激损伤和凋亡,伴随SIRT1信号通路的激活。用Sirtinol抑制SIRT1信号通路后Cur的心肌保护作用明显减弱。结论 Cur通过激活SIRT1信号通路,抑制氧化应激损伤和凋亡,从而改善脓毒症引起的心肌损害。

Objective To investigate the protective effect of curcumin pretreatment on myocardial damage in septic mice and whether SIRT1 signaling pathway mediates the cardioprotective effect of curcumin. Methods A sepsis model was established by cecal ligation and perforation in mice. Curcumin( 100 mg/kg,i.g.) and SIRT1 specific inhibitor Sirtinol( 5 mg/kg,i.p.) were administered for consecutive 3 days before surgery. Forty-eight hours after cecal ligation and perforation,the cardiac systolic and diastolic function of the mice were detected by Millar catheter technique. Malondialdehyde content and the activities of superoxide dismutase and glutathione peroxidase were detected by commercially available kits. Myocardial apoptotic ratio was detected by TUNEL staining. The expression of SIRT1 signaling pathway and apoptosis-related proteins were detected by Western Blotting. Results Compared with the Sham group,the systolic and diastolic function of the mouse heart were significantly impaired,the myocardial malondialdehyde content was increased,the activities of superoxide dismutase and glutathione peroxidase were significantly reduced,the apoptotic ratio and the expression of Bax and Caspase 3 were significantly increased,and the expression of Bcl-2 was significantly decreased after cecal ligation and perforation( P <0.05). Curcumin pretreatment significantly improved cardiac function,inhibited myocardial oxidative stress damage and apoptosis,and accompanied by activation of SIRT1 signaling pathway. Inhibition of SIRT1 signaling pathway using Sirtinol largely abolished the cardioprotective effects of curcumin. Conclusion Curcumin ameliorates septic cardiomyopathy through inhibiting oxidative stress injury and apoptosis in a SIRT1-dependent manner.