DSPE-PEG-胆酸修饰水飞蓟宾脂质体对CCl_4致急性肝损伤小鼠的保护作用研究

Protective effect of DSPE-PEG-cholic acid modified silybin liposome on CCl_4-induced acute hepatic injury in mice

目的:研究DSPE-PEG-胆酸修饰水飞蓟宾脂质体对四氯化碳(CCl4)所致小鼠急性肝损伤的保护作用。方法:将48只雄性ICR种小鼠随机分成6组:正常对照组、CCl_4肝损伤模型组、水飞蓟宾胶囊剂组、水飞蓟宾修饰脂质体低、中、高剂量组。采用腹腔注射CCl4致小鼠急性肝损伤模型,测定小鼠血清谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST);测定肝脏丙二醛(malondialdehyde,MDA)含量,谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)含量和超氧化物歧化酶(superoxide dismutase,SOD)活力,计算肝指数,并观察肝组织病理学变化。结果:与CCl_4模型组比较,各治疗组小鼠肝脏指数、血清ALT和AST活性不同程度降低(P<0.05);肝组织匀浆中MDA,GSH-Px,SOD活力不同程度升高(P<0.05);病理切片表明小鼠肝损伤不同程度减轻,而且脂质体组比胶囊剂组有较好改善。结论:DSPE-PEG-胆酸修饰水飞蓟宾脂质体对CCl_4所致小鼠急性肝损伤有显著的保护作用,且高于水飞蓟宾胶囊剂组。

Objective： To determine the protective effect of DSPE-PEG-cholic acid modified silybin liposome on CCl4-induced acute hepatic injury in mice. Methods： 48 male ICR mice were randomly divided into 6groups： normal control group,CCl4 induced liver damage model,silybin capsule as positive group,modified liposome with low,medium and high dose group. Establishing acute liver injury in mice model by intraperitoneal injection of CCl4,alanine aminotransferase（ ALT） and aspartate aminotransferase（ AST） in plasma,and malondialdehyde（ MDA）,glutathione peroxidase（ GSH-Px） and superoxide dismutase（ SOD） activity in the liver were determined; the liver index were calculated; hepatic histopathological changes were observed. Results：Compared with CCl4 model group,the liver index,and ALT and AST activities in serum significantly decreased（ P〈0. 05）; MDA,GSH-Px and SOD activity in the liver homogenate significantly increased（ P〈0. 05） after the silybin liposome treatment. Histopathologic examination showed that silybin liposome alleviated the liver injury,and high dose（ 5 mg·kg^-1） was more effective. Conclusion： DSPE-PEG-cholic acid modified silybin liposome has significant protective effect on acute liver injury induced by CCl4 in mice,and is more potent than silybin capsule.