镉诱导小鼠急性肝损伤模型的研究

目的 通过腹腔注射氯化镉( CdCl2 )建立小鼠急性肝损伤模型,初步阐明其分子机制. 方法 以4 mg/kg CdCl2腹腔注射小鼠,观察各时间点小鼠肝组织病理变化和血清丙氨酸氨基转移酶( ALT)、天冬氨酸氨基转移酶( AST)的变化,探索CdCl2 引起明显肝损伤的染毒时间;以1、2、4 mg/kg CdCl2 对小鼠腹腔注射染毒,筛选出CdCl2 诱导急性肝损伤的最佳染毒剂量;检测血清丙二醛( MDA)以及肝匀浆MDA、一氧化氮( NO )、谷胱甘肽( GSH )、谷胱甘肽过氧化物酶( GSH-PX)含量,观察氧化应激在CdCl2 诱导的小鼠肝损伤中的作用. 结果 以4 mg/kg CdCl2 腹腔注射18 h后,肝脏组织出现片状坏死,肝细胞严重气球样变,血清ALT和AST明显升高. 此外,与对照组比较,CdCl2 处理18 h后,血清与肝脏MDA及肝脏NO水平显著升高,肝脏GSH、GSH-PX活性明显降低. 结论 4 mg/kg CdCl2 腹腔注射18 h后可成功建立小鼠急性肝损伤模型,其发生可能与MDA和NO升高,肝组织GSH含量、GSH-PX活性降低相关.

Establishment of mouse model of acute liver injury induced by cadmium chloride

Objective To establish the mouse model of acute liver damage induced cadmium chloride and elucidate the mechanism of Cd-induced-liver injury. Methods The adult male mice were intraperitoneally ( i. p. ) injected with a single dose of CdCl2 (4 mg/kg) and killed at different time(6, 12, 18, 24 h) after Cd treatment, or admin-istrated with different doses of CdCl2 (1, 2 or 4 mg/kg) i. p. and sacrificed at 18 h after Cd exposure. The control group received only equal volumes of normal saline. Histopathology of liver tissues, serum of ALT, AST and MDA, and MDA,NO,GSH,GSH-PX of liver tissues were observed. Results 18 hours after the treatment of using 4 mg/kg dosage, i. p, liver tissues appeared visible pathological changes with severe ballooning degeneration and necro-sis, the levels of ALT and AST in serum were obviously higher. In addition, at 18 h after Cd treatment, the levels of MDA and NO in liver tissues significantly increased in the cadmium group, however, the level of GSH and the activity of GSH-PX in liver tissues significantly decreased. Conclusion A mouse model of acute liver injury is successfully established by intraperitoneal injection with 4 mg/kg CdCl2 at 18 hours after Cd treatment. The mecha-nism might be associated with the increase of MDA and NO and the decrease of the level of GSH and the activity of GSH-PX in liver tissues.