一氧化碳释放分子对大鼠脓毒症诱导急性肾损伤的保护作用

The Protection of Carbon Monoxide Releasing Molecules on Sepsis with Acute Kidney Injury in Rats

目的:观察一氧化碳释放分子(CORM-2)对脓毒血症大鼠急性肾损伤的影响。方法:采用盲肠结扎穿孔术诱导大鼠脓毒症肾损伤模型,64只雄性SD大鼠随机平均分为4组(n=16),假手术组(Sham组)、Sham组+CORM-2组,盲肠结扎穿孔(CLP)组及CLP+CORM-2组。CORM-2治疗组为盲肠结扎穿孔术后给予腹腔注射10mg/kg剂量CORM-2。观察各组大鼠3d累积生存率,术后12 h测定肾脏组织中肌酐和尿素氮水平,同时检测IL-1β及TNF-α水平,观察各组大鼠24 h时间点肾脏组织病理学变化。结果:与对照组(Sham组,Sham+CORM-2组)相比,CLP组及CLP+CORM-2组大鼠生存率下降,肾组织肌酐、尿素氮升高,IL-1β及TNF-α水平升高(P<0.05)。但与CLP组相比,CLP+CORM2可提高大鼠的3d累积生存率,并改善脓毒症大鼠肾组织损伤,降低肾组织中IL-1β及TNF-α水平(P<0.05)。结论:CORM-2对脓毒症大鼠急性肾损伤有保护作用,其机制可能与CORM-2抑制脓毒症致肾损伤大鼠的炎性反应相关。

Objective ：To investigate the effects of carbon monoxide releasing molecules（CORM-2） on sepsis with acute kidney injury in rats. Methods ： Sepsis kidney injury model was induced by cecal ligation and puncture 64 male SD rats. The rats were randomly divided into four groups（n = 16）, sham-operated group（Sham group）, Sham group ＋ CORM-2 group, cecal ligation and puncture（CLP） group and CLP ＋ CORM-2 group. CORM-2 treatment group were given intraperitoneal injection of 10 mg / kg dose of CORM-2 after cecal ligation and puncture. The three days cumulative survival rate was observed in four groups. The levels of blood urea nitrogen, creatinine, IL-1β and TNF-α of kidney tissue were detected after 12 h of CLP, and the renal histopathological changes were observed after24 h of CLP in each group. Results ： Compared with the control group（Sham group, Sham ＋ CORM-2 group）, CLP group and CLP ＋ CORM-2 group were reduced survival rate and kidney creatinine, blood urea nitrogen, IL-1β and TNF-α significantly increased（P〈0.05）. however, compared with CLP group, CLP ＋ CORM-2 can improve the 3-day ssurvival rate of the rats and reduce septic rat kidney tissue injury, reduced renal tissue IL-1β and TNF-α levels（P〈0.05）. Conclusion ：CORM-2 has a protective effect on septic acute kidney injury through inhibiting the inflammatory response in sepsis-induced renal injury in rats.