LPS预处理减轻CCl_4诱导的慢性肝损伤

LPS preconditioning relieves chronic liver injury induced by carbon tetrachloride

目的:探讨脂多糖(LPS)预处理对四氯化碳(CCl4)诱导的肝损伤的影响及相关的信号转导分子的变化。方法:雄性Wistar大鼠随机分为正常对照组、肝损伤组和LPS预处理组。肝损伤组和LPS预处理组经皮下注射CCl4并同时饲以高脂饮食造模,于实验第4周末处死动物,取血浆测定内毒素水平和ALT活性;取肝组织测定TNF-α水平;Western blotting测定肝组织中TLR4、p38、p-p38、IκΒ、NF-κΒp65表达;制备肝脏切片,观察肝脏病理改变。结果:LPS预处理可明显减轻CCl4所致肝损伤,经LPS预处理动物血浆ALT活性显著低于肝损伤组(P<0.01);肝匀浆的TNF-α测定结果表明,LPS预处理组TNF-α含量明显低于肝损伤组(P<0.01)。LPS预处理组TLR4、p-p38、NF-κΒ的表达显著低于肝损伤组,而IκΒ表达显著高于肝损伤组。结论:LPS预处理可以减轻CCl4诱导的肝损伤,LPS预处理引起相关信号转导通路发生了改变,致使致炎因子分泌减少可能是其作用机制。

AIM： To investigate the effect of lipopolysaccharides （LPS） preconditioning on CCl4 - induced liver injury and the change of LPS signal transduction. METHODS ： The male Wistar rats were divided randomly into liver - injury group, which were injected with CCl4 5 mL/kg first, three days later were injected 0. 3 mL 40% CCl4 and 60% olive oil. Animals in LPS preconditioning group were injected with LPS 0. 5 mg/kg before the day CCl4 was given. Rats received high fat diet were as liver injury group, and normal control group received normal diet. The lymphocytes infiltrated in the liver tissue were counted. The endotoxin and ALT level in rat plasma, TNF - α content and expressions of TLR4, p38, -p38, IkB, NF - kB in the rat livers were also determined. RESULTS： The lymphocytes in liver slice and ALT level of the plasma in LPS preconditioning group were lower significantly than those in the liver injury group, and the expressions of TLR4, p - p38, NF - kB in the liver were the same. In contrast, the expression of IkB was higher. CONCLUSION： LPS preconditioning relieves obviously CCl4 - induced chronic liver injury. The mechanism may be associated with change of signal transduction of LPS, which results in decrease of pre - inflammatory cytokines.