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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),6 h后按8 ml/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,12 h后再给予GalN/LPS染毒。染毒12 h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Hb CO的水平维持在8%~12%达12 h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。
Objective To study the protective effect of low concentration of carbon monoxide (CO) on acute liver injury in mice induced by GalN and lipopolysaccharide (LPS). Methods Wild type C57BL / 6 mice were divided into normal control group, CO control group, liver injury group and liver injury + CO group (GalN / LPS + CO group), with 8 mice in each group. Mice with liver injury were injected intraperitoneally with GalN (550 mg / kg) and LPS (15 mg / kg). CO control group: The pure CO gas (15 ml / kg) was injected intraperitoneally and then injected again at the dose of 8 ml / kg after 6 hours. During the period, the level of carboxyhemoglobin (HbCO) was detected dynamically. GalN / LPS + CO group: CO gas was injected by the same method, and GalN / LPS was given after 12 h. The indexes of liver injury, pathological changes, apoptosis and inflammatory cytokines (IL-1b, IL-6, IL-10 and TNF-a) Results Compared with normal control group and CO control group, the levels of ALT, AST and T-BIL in plasma increased significantly in mice exposed to GalN / LPS, and a large number of hepatocytes were degenerated and necrotic . The intraperitoneal injection of low concentration of CO in mice maintained the level of blood Hb CO above 8% ~ 12% for more than 12 h, significantly decreased the levels of ALT, AST and TBIL induced by GalN / LPS and significantly reduced the apoptosis of hepatocytes And inhibit the level of inflammatory cytokines. Conclusion Exogenous low concentration of CO can reduce GalN / LPS-induced acute liver injury in mice, the mechanism may be related to the reduction of apoptosis and cytokine levels.