外源性低浓度一氧化碳对小鼠急性肝损伤的保护作用研究

目的 研究外源性低浓度一氧化碳(CO)对D-氨基半乳糖(GAlN)和脂多糖(LPS)联合诱导小鼠急性肝损伤的保护作用及机制.方法 将野生型C57BL/6小鼠分为正常对照组、CO对照组、肝损伤组和肝损伤+CO组(GalN/LPS+CO组),每组8只.肝损伤组小鼠经腹腔注射GalN(550 mg/kg)和LPS(15 mg/kg)造模.CO对照组:经腹腔注射纯品CO气体(15 ml/kg),6h后按8ml/kg剂量再注射一次,期间动态检测碳氧血红蛋白(HbCO)的水平变化.GalN/LPS+CO组:按同样方法注射CO气体,12h后再给予GalN/LPS染毒.染毒12h后检测各组小鼠的肝损伤指标、病理学指标、细胞凋亡和炎症因子(IL-1b、IL-6、IL-10和TNF-a)的水平变化.结果 小鼠给予GalN/LPS后发生严重急性肝损伤;与正常对照组或CO对照组相比,染毒组小鼠血浆ALT、AST和T-BIL水平均明显升高,大量肝细胞变性、坏死.小鼠腹腔注射低浓度CO使血HbCO的水平维持在8％～12％达12h以上,显著降低GalN/LPS染毒导致的ALT、AST和TBIL水平升高,同时明显减轻肝细胞凋亡和抑制炎症因子水平.结论 外源性低浓度CO可以减轻GalN/LPS诱导的小鼠急性肝损伤,其机制可能与降低细胞凋亡和细胞因子的水平有关.

Low dose carbon monoxide intra-peritoneal injection provides protection against GalN/LPS-induced acute liver injury in mice

Objective To study the protective effects of exogenous CO at low dose in a murine model of acute liver damage induced by D-galactosamine (GAIN) and lipopolysaccharide (LPS).Methods Exogenous CO gas was administered to mice via intra-peritoneal injection (first at a dose of 15 ml/kg and then 6 h later,8 ml/kg),which caused a significant elevation of blood carboxyhemoglobin (HbCO) levels of up to 8％-12％ for more than 12 h.GalN/LPS were given to induce acute liver damage in mice after CO exposure.The liver function,histological indexes,cell apoptosis,and the relevant inflammatory mediators were evaluated.Results It showed that GalN/LPS induced severe liver injury in mice,whereas CO injection remarkably attenuated hepatocellular damage.CO exhibited anti-apoptotic and anti-inflammatory effects which were characterized by a notable inhibition of hepatocyte apoptosis and a reduction of pro-inflammatory cytokines in mice.Conclusion Exogenous CO provides protective effects against acute liver damage in mice,mainly dependent on its anti-apoptotic and anti-inflammatory properties.