CAPE-NO_2预处理对CCl_4引起的小鼠肝损伤的保护作用

Protective effect of p-nitro caffeic acid phernethyl ester on liver injury induced by CCl_4 in mice

目的研究对硝基咖啡酸苯乙酯(CAPE-NO2)对CCl4诱导的小鼠化学性肝损伤的保护作用。方法小鼠分为7组,每组10只。分组:正常组,CAPE-NO2(2.0 mg/kg)组,模型组,CAPE(2.0 mg/kg)+CCl4组,CAPE-NO2(2.0 mg/kg)+CCl4组,CAPE-NO2(1.0mg/kg)+CCl4组,CAPE-NO2(0.5mg/kg)+CCl4组。各组腹腔注射给药15d,正常组和模型组给生理盐水0.1mL/10g。第15天给药结束后,正常组和CAPE-NO2组腹腔注射橄榄油溶液(0.1 mL/10g),其余各组腹腔注射0.15%CCl4橄榄油溶液(0.1mL/10g)。测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)活性、三酰甘油(TG)水平,肝组织匀浆谷胱甘肽过氧化物酶(GSH-Px)活性、过氧化氢酶(CAT)活性。取肝左叶经10%多聚甲醛固定,进行组织病理学检查和TUNEL染色。结果 CAPE-NO2能显著降低CCl4诱导的肝损伤小鼠血清ALT、AST活性、TG水平,升高小鼠肝组织中CAT、GSH-Px的活性,且呈药效剂量依赖性。CAPE-NO2能明显减少肝细胞损伤和降低肝细胞凋亡率,且作用强于CAPE。结论 CAPE-NO2对小鼠化学性肝损伤具有一定的保护作用,机制可能与增强肝细胞抗氧酶的水平,提高机体清除自由基能力和抑制细胞凋亡有关。

Objective To investigate the protective effect of p-nitro caffeic acid phernethyl ester（CAPE-NO2）pretreatment on liver injury induced by CCl4 in mice.Methods A total of 70 mice were divided into 7groups,normal group,CAPE-NO2（2.0mg/kg）group,model group,CAPE（2.0mg/kg）＋CCl4group,CAPE-NO2（1.0mg/kg）group＋CCl4group and CAPE-NO2（0.5mg/kg）＋CCl4group.Each group was given the intraperitoneal medication for 15 d.Normal saline 0.1mL/10 g was given in the normal group and the model group.After15 dmedication,the normal group and the CAPE-NO2 group were itraperitoneally injected by olive oil solution 0.1mL/10 g,the other groups by 0.15% CCI4-olive oil solution（0.1mL/10g）.The serum ALT,AST and TG levels and GSH-Px activity and CAT activity in liver homogenate were measured.The left hepatic lobe was taken and fixed by 10%paraformaldehyde for conducting the histopathological examination and TUNEL staining.Results CAPE-NO2 could significantly reduce serum ALT and AST activities and TG level in mice with CCl4 induced liver damage,and increased the CAT and GSH-Px activities in liver tissue with a dose-dependent manner.CAPE-NO2 could significantly reduce the hepatocellular injury and decreased the hepatocellular apoptosis rate,moreover its effect was stronger than that of CAPE.Conclusion CAPE-NO2 has certain protective effect on mice chemical liver injury,its mechanism might be associated with enhancing the antioxidase level of liver cells and increase the capability for scavenging free radicals and inhibiting apoptosis.