氨基葡萄糖对CCl4所致小鼠肝损伤的改善作用

Protective effects of D-glucosamine against carbon tetrachloride-induced liver damage in mice

目的:研究氨基葡萄糖(GlcNH2)的抗氧化能力和对CCl4诱导的小鼠肝损伤的改善作用。方法:雄性昆明种小鼠24只随机均分为3组。GlcNH2组每dGlcNH2(1.5g/kg)灌胃;CCl4损伤组和空白对照组每d给予相应体积的生理盐水。前2组于第12天末次给药3h后腹腔注射CCl4(20mg/kg),24h后眼球取血,分别测定各组小鼠血清中丙氨酸转氨酶(ALT)和天门冬氨酸转氨酶(AST)的活性,处死动物后取肝组织,测定肝匀浆中总抗氧化能力(T-AOC),总巯基(T-SH)、非蛋白结合巯基(NP-SH)、金属硫蛋白(MT)、丙二醛(MDA)含量和DNA损伤情况。结果:小鼠腹腔注射CCl424h后,血清AST和ALT活性明显提高,引起肝脏脂质过氧化反应,巯基含量降低,T-AOC减弱,诱发基因毒性。提前连续12d灌胃给予GlcNH2能够显著诱导MT的表达,体内的抗氧化防御系统随之增强以抵抗CCl4诱导的氧化损伤。GlcNH2组与CCl4损伤组相比,AST、ALT活性和MDA含量均明显下降,T-AOC和T-SH、NP-SH、MT含量与CCl4组相比均明显提高。DNA电泳结果显示,GlcNH2组与CCl4组的DNA链都形成一系列1000bp大小左右的DNA片段。结论:GlcNH2具有抗氧化能力,其对CCl4诱导的小鼠肝损伤有较为明显的改善作用,但是不能减轻DNA的氧化性损伤。

Aim ： To study the antioxidant and hepatoprotective effects of D-glucosamine （ GlcNH2 ） against carbon tetrachloride （CCl4） induced mice liver damage. Methods：Male ICR mice were randomly divided into 3 groups with 8 animals each. Mice of experimental group were pretreated GlcNH2 （ 1. 5 g/kg body weight） once daily while mice of control group and CCl4 group received the same dose saline only. CCl4 （20 mg/kg body weight） was injected 3 h after the last administration 12 days later. 24 hours after the administration of CCl4 , eyeball blood was collected and serum was separated for determination of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） activities. Then the animals were sacrificed and livers were dissected out. Total antioxidant capabilities （T-AOC）, total sulfhydryl （T-SH）, nonprotein sulfhydryl （NP-SH） , metallothionein （MT） and malondialdehyde （MDA） quantification in liver homogenate were measured and qualitative analysis of liver DNA fragmentation was undertaken. Results： CCl4 administration induced marked increase in serum AST and ALT activities, primed liver lipid peroxidation, depleted sulfhydryl content, impaired T-AOC and induced genotoxicity 24 h after administration. Pretreatment with GlcNH2 for 12 consecutive days prior to CCl4 challenge significantly induced MT expression. Thus, the antioxidant defensive system in the body was strengthened to counteract the oxidative damage induced by the succedent CCl4 administration. Serum AST and ALT activities and MDA formation in GlcNH2 pretreated group efficiently decreased compared to CCl4 group. On the contrary, T-SH, NP-SH and MT contents and T-AOC improved significantly. DNA isolated from both the GlcNH2 group and the CCl4 group similarly showed the fragmentation of about 1 000 bp by agarose gel electrophoresis. Conclusion ： The results indicated that pretreatment with GlcNH2 could efficiently improve the antioxidant activity and protect mice against CCl4 induced liver damage but the oxidative damage to DNA could not be mitigated.