血红素加氧酶-1/一氧化碳在急性肝损伤中的变化

Changes of heine oxygenase-1 and its product carbon monoxide in acute liver injury

目的研究急性肝损伤时大鼠肝脏血红素加氧酶-1(HO-1)/一氧化碳(CO)系统的变化规律及其病理生理意义。方法大鼠经腹腔注射四氯化碳建立急性肝损伤模型,动态测定肝脏HO酶活性和蛋白的表达情况,测定肝脏CO含量以及血清ALT、AST水平和肝组织SOD、MDA变化。结果四氯化碳可成功诱导大鼠急性肝损伤,使血清ALT、AST水平以及肝组织MDA浓度升高,SOD活性下降,与对照组相比差异具有统计学意义。染毒后大鼠肝脏HO活性明显增强,和对照组相比差异具有统计学意义;western blot和免疫组化结果均证实,HO-1蛋白在染毒后表达显著增高,并呈一定的时间依赖方式。此外,正常大鼠肝脏CO浓度极低,染毒后6 h则开始升高,和对照组相比差异具有统计学意义,这与HO-1表达情况相一致。结论大鼠急性肝损伤后出现HO-1活性增加和蛋白表达持续上调以及CO浓度迅速增高,提示HO-1/CO系统参与急性肝损伤的病理生理过程,其表达增加可能有利于机体抗氧化性损伤。

Objective To investigate dynamic changes of heine oxygenase-1 and carbon monoxide in acute liver injury induced by carbon tetrach loride （CCl4） in rats. Method Male SD rats were randomly allocated to induce acute liver injury by CCl4 injection. Hepatic HO activity was examined at different time point following CCl4 treatment. Expression and location of HO-1 protein was determined by western blot and methods. Serum ALT, AST levels and hepatic SOD, MDA concentrations were also analyzed. Results Administration of CCl4 to rats caused a marked hepatic damage, characterized by significant elevation of serum ALT, AST levels and liver MDA content combined with a remarkable reduction in liver SOD activity. HO activity was elevated significantly in a time-dependent manner after CCl4 injection, while the expression of HO-1 protein increased remarkably from 6 to 36 hours. CO concentration in the liver homogenate of control rats remained very low but was elevated significantly after CC14 treatment, which was in accordance with changes of HO-1. Conclusions HO-1 activity and protein expression as well as CO production are higher in rats with acute liver injury induced by CCl4 than in control group. HO-1/CO system plays an important role in the pathogenesis of acute hepatic damage and may have potent protective effect against liver injury.