不同剂量维生素C对细菌内毒素致急性肝损伤的影响

Effect of two different doses of vitamin C on the acute hepatic injury induced by lipopolysaccharide

目的比较不同剂量维生素C(VC)对细菌内毒素(LPS)致小鼠急性肝损伤的影响。方法一次性腹腔注射LPS(4 mg/kg),造成急性肝损伤模型,于LPS处理前0.5 h分别灌胃给予两种不同的VC剂量(100 mg/kg和500 mg/kg),LPS处理后8 h和24 h分别处死小鼠,测定血清丙氨酸氨基转移酶(ALT)、天门冬氨酸转氨酶(AST)活性和肝脏还原型谷胱甘肽(GSH)、丙二醛(MDA)含量,观察肝脏形态学变化,采用Western blot法检测肝脏组织硝基酪氨酸(3-NT)蛋白表达水平。结果与对照组相比,LPS模型组小鼠血清ALT、AST活性均明显升高,肝脏MDA含量明显增加,GSH含量明显降低,3-NT蛋白水平明显升高,肝组织细胞肿胀明显,可见肝细胞点状坏死等病理学改变;与LPS模型组相比,100 mg/kg VC预处理可部分逆转LPS引起的上述改变,而单纯500 mg/kg VC处理组小鼠肝脏GSH含量虽有一定程度的升高,但未达单纯100 mg/kg VC处理组小鼠水平,且其他指标与LPS模型组比较差异无统计学意义。结论 VC的抗氧化及肝损伤保护作用与其剂量有着密切的关系,应合理正确地应用。

Objective To observe the effects of different doses of vitamin C （VC） on lipopolysaceharidc （LPS） -in- duced acute hepatic injury in mice. Methods The acute hepatic injury model for the mice was administered with a single dose of LPS（4 mg/kg, i.p. ）, and the mice were pretreated with two different doses of vitamin C （100 rag/ kg or 500 mg/kg, i.g. ） at 30 rain before LPS and sacrificed at 8 h or 24 h after LPS administration. Serum was analyzed for the activity of alanine aminotransferase （ALT） and aspertate aminotransferase （ AST）, livers were dis- sected for measurements of reduced glutathione （GSH） contents, malondialdehyde （MDA） contents, pathological change and the protein expressions of 3-NT by Western blot. Results Compared with the control group, LPS sig- nificantly upregulated serum ALT, AST activities, significantly increased MDA content and reduced GSH content in liver, the protein expressions of 3-NT were upregulated, and liver pathological changes aggravated. Compared with model group, VC（100 mg/kg ） improved part of the above change by LPS; although VC（500 mg/kg ） could at- tenuate hepatic GSH depletion, but not as effective as VC （100 mg/kg ）, and other indicators was not changed sig- nificant. Conclusion The antioxidant and the protective effect of VC on liver injury depend on its dose. It must be used rationally.