栀子中京尼平甙对CCl4急性小鼠肝损伤保护作用的生化机理研究

预先给小鼠灌胃不同剂量的京尼平甙后,以四氯化碳造模,通过测定小鼠血清中丙氨酸氨基转移酶(ALT)、天氡氨酸氨基转移酶(AST)以及肝脏内GSH的含量并制作组织病理切片,研究了京尼平甙对四氯化碳肝损伤小鼠的保护作用,结果表明,京尼平甙能抑制四氯化碳肝中毒小鼠血清中ALT和AST的活性以及增加肝脏内GSH的含量.然后研究了京尼平甙对正常小鼠肝微粒体内细胞色素P4502E1和细胞色素P4503A活性的影响以及肝脏内谷胱甘肽(GSH)系统的影响,表明京尼平甙对正常小鼠肝微粒体内CYP4502E1具有明显的抑制作用,并能增强肝脏内谷胱甘肽还原酶(GR)以及谷胱甘肽-S-转移酶活性.以上3个酶与自由基形成以及清除有关.图1表3参16

BIOCHEMICAL MECHANISM OF HEPATIC PROTECTIVE EFFECT OF GENIPOSIDE ON LIVER-INJURED MICE INDUCED BY CCl4

Kunming mice (KM) were treated with geniposide and with CCl_ 4. Then, the hepatic protective effect of geniposide was thus studied by measuring the activities of serum ALT and AST, the content of GSH of the mice by histopathological examination. The results showed that geniposide could suppress the increase of ALT and AST, and decrease GSH. In order to understand the possible biochemical mechanism of this effect, normal mice were treated with different concentrations of geniposide, and then the activity of CYP450 2E1 in the liver microsome and those of GST and GR in liver were assayed. After the mice were treated with 50 mg/kg, 100 mg/kg or 150 mg/kg of geniposide once a day for 5 days, the activity of CYP450 2E1 decreased and those of GST and GR increased significantly compared with the control groups. These results suggested that geniposide protect hepatic damage by decreasing the activities of CYP450 2E1 and increasing those of GR and GST, all of which are closely related to radical elimination. Fig 1, Tab 3, Ref 16