抑制性寡脱氧核苷酸对实验性肝损伤细胞因子的影响

The Effect of Suppressive Oligonucleotides on Cytokine Expression of Concanavalin A-induced Liver Injury in Mice

探讨抑制性寡脱氧核苷酸(suppressive oligonucleotides,Sup ODN)对刀豆蛋白A(Con A))诱导的小鼠实验性肝损伤的保护作用.实验采用Balb/C小鼠40只,随机分4组,分别为生理盐水(NS)组、对照寡脱氧核苷酸(control oligonucleotides,Con ODN)组、环孢菌素A(cyclosporin A,CsA)组、Sup ODN组.Con A(20mg/kg)尾静脉注射Balb/C小鼠,2h时腹腔给药,给药8h时观察小鼠的血清丙氨酸氨基转移酶(ALT)活性、死亡率;检测血清TNF-α、IFN-γ、TIL-4水平;RT-PCR检测肝组织TNF-α、IFN-γ mRNA的表达;并观察肝组织的病理改变.发现Sup ODN组与NS组、Con ODN组相比,ALT活性明显降低(P<0.01);与NS组、Con ODN组和CsA组比较,IFN-γ明显降低(P<0.01),IL-4明显升高(P<0.01),TIFN-γ mRNA表达亦显著减少;而且Sup ODN可明显减轻肝脏炎性细胞浸润和肝细胞坏死(P<0.05).实验表明Sup ODN对Con A小鼠实验性肝损伤有明显保护作用.

To investigate the protective effect of suppressive oligonucleotides （Sup ODN） on concanavalin A （Con A）-induced liver injury in mice. The adopted Forty Balb/C mice were randomly divided into 4 groups, normal saline （NS） group, control oligonucleotides （Con ODN） group, cyclosporin A （CsA） group and Sup ODN group. Mice in each group were injected with Con A （20 mg/kg） via the tail vein. NS（0.3 mL per mouse）, Con ODN （20 mg/kg）, CsA （130 mg/kg） or Sup ODN （20 mg/kg） was injected intraperitoneally at 2 hours after Con A injection. Death rate of each group at 8 hours after intraperitoneal injection was calculated and survived mice were killed in order to get blood and liver samples. Activity of aminnotransferase （ALT） was tested and levels of TNF-α, IFN-γ and IL-4 were detected by ELISA. Expression of TNF-α and IFN-γ mRNA in liver tissue was detected by RT-PCR. Histopathological examination for liver was also performed. It was found that ALT activity in Sup ODN group was significantly lower compared with NS or Con ODN group respectively （P 〈 0.01）. Decreased level of IFN-γ and its mRNA expression and increased level of IL-4 in Sup ODN group were marked compared with NS, Con ODN and CsA group （P 〈 0.01 ）. Hepatic histopathology changes were alleviated in Sup ODN group compared with NS and Con ODN group. The research indicated Sup ODN has a certain protective effect on Con A-induced mice liver injury.