姜黄素抵抗脓毒症心肌损伤新机制探究

Study of novel mechanism of curcumin against myocardial injury induced by sepsis:SIRT3 and related signaling pathways

目的探究姜黄素是否通过激活线粒体去乙酰化酶3(SIRT3)信号通路逆转脓毒症心肌损伤。方法通过盲肠结扎穿孔构建小鼠脓毒症模型。SIRT3特异性抑制剂3-TYP(50 mg/kg)和姜黄素(80 mg/kg)于术前3 d每日通过腹腔注射给予,共给药3次。术后2 d检测心脏功能、氧化应激损伤和凋亡相关指标、SIRT3信号通路表达情况。结果与假手术组小鼠相比,脓毒症小鼠心肌组织内SIRT3表达明显降低,伴随其下游分子超氧化物歧化酶2(SOD2)的乙酰化水平明显增加。此外,与假手术组小鼠相比,脓毒症小鼠心功能明显受损,心肌氧化应激和凋亡水平明显提高。姜黄素预处理可以明显改善脓毒症小鼠心脏功能,抑制心肌氧化应激损伤和凋亡并激活SIRT3信号通路。而抑制SIRT3信号通路后,姜黄素的心肌保护作用明显减弱。结论SIRT3/SOD2信号通路介导姜黄素抗氧化应激损伤和细胞凋亡,进而抗脓毒症心肌损伤的作用。

Objective To investigate whether curcumin(Cur)can reverse sepsis-induced myocardial injury by activating SIRT3 signaling pathway.Methods A mouse sepsis model was constructed by cecal ligation and puncture(CLP).The SIRT3 specific inhibitor 3-TYP(50 mg/kg/day)and curcumin(80 mg/kg/day)were administered by intraperitoneal injection three times before CLP surgery.Cardiac function,oxidative stress injury index,apoptosis-related indicators and the expression of SIRT3 signaling were measured 2 days after CLP surgery.Results Compared with the sham-operated mice,the expression of SIRT3 in myocardial tissue of septic mice was significantly impaired,accompanied by a significant increase in the level of acetylated superoxide dismutase 2(SOD2).In addition,compared with sham-operated mice,cardiac function was significantly impaired,and myocardial oxidative stress and apoptosis levels were significantly increased in septic mice.Curcumin pretreatment could significantly improve cardiac function,in hibit myocardial oxidative stress damage and apoptosis,and activate the SIRT3 signaling pathway in mice with sepsis.After inhibiting the SIRT3 signaling pathway,the myocardial protection of curcumin was significantly abolished.Conclusion The SIRT3/SOD2 signa ling pathway mediates the anti-oxidative and anti-apoptotic effects of curcumin,which in turn protects against myocardial injury in duced by sepsis.