橙皮苷对急性肝损伤模型小鼠肿瘤坏死因子-α和干扰素-γ表达的影响

Influence of Hesperidin on the Expression of TNF-α and IFN-γ in Concanavalin Ainduced Acute Liver Injury in Mice

目的研究橙皮苷对刀豆蛋白A(Con A)致小鼠急性肝损伤的保护作用及其对肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ)表达的影响。方法 72只SPF级C57BL/6雄性小鼠,随机均分为正常对照组、模型对照组和橙皮苷组。橙皮苷组给小鼠连续灌胃橙皮苷悬浊液1 000 mg·kg-1,灌胃10 d,模型对照组灌胃等量0.5%羧甲基纤维素钠,模型对照组和橙皮苷组均用Con A诱导小鼠急性肝损伤模型,测定血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)的含量;苏木精-伊红(HE)染色检查肝组织病理变化,反转录-聚合酶链反应(RT-PCR)法检测肝组织TNF-α和IFN-γmRNA水平,酶联免疫吸附测定(ELISA)法检测血清TNF-α和IFN-γ水平。结果橙皮苷预处理后,与模型对照组比较,橙皮苷组ALT和AST水平显著降低(P<0.01),肝细胞坏死及炎性细胞浸润明显减轻,肝组织TNF-α和IFN-γmRNA表达明显下调(P<0.01)。橙皮苷组血清TNF-α和IFN-γ水平2 h分别为(717.05±205.22),(611.06±92.82)pg·m L-1,6 h分别为(811.56±167.47),(786.19±215.44)pg·m L-1。橙皮苷组TNF-α和IFN-γ水平较模型对照组明显降低(P<0.01),但Con A注射6 h,橙皮苷组TNF-α水平与模型对照组比较,差异无统计学意义(P>0.05)。结论橙皮苷预处理对Con A致小鼠急性肝损伤具有保护作用,其作用机制与其抑制TNF-α和IFN-γ的表达有关。

Objective To explore the protective effect of hesperidin pretreatment on concanavalin A （Con A）-induced acute liver injury and the effect on expression of TNF-α and IFN-γ. Methods Seventy-two SPF C57BL/ 6 mice were randomly divided into three groups： normal control group, model control group and hesperidin group. Acute liver injury model was established by injected with Con A. The hesperidin group was treated intragastrically with 1 000 mg·kg-1 hesperidin for 10 days. Model control group was treated intragastrically with the same volume of 0. 5% of sodium carboxymethyl cellulose. Serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （ AST） were measured. Pathological changes in hepatic tissue were observed under microscope. The expression of TNF-α and IFN-γ mRNAs in hepatic tissue was measured by reverse transcription polymerase chain reaction （ RT-PCR）. The contents of TNF-α and IFN-γ in serum were detected by ELISA. Results Compared with model control group, the contents of ALT and AST in serum were significantly decreased （P〈0. 01） in hesperidin group. Pathological changes in hepatic tissue were markedly improved. The expression of TNF-α and IFN-γ in the hepatic tissues and serum were significantly downregulated （P〈0. 01）. The concentrations of TNF-α and IFN-γ in hesperidin group were （717. 05±205. 22） and（611. 06±92. 82）pg·mL-1 in 2 h,（811. 56±167. 47）and（786. 19±215. 44）pg·mL-1 in 6 h. Compared with model control group, the expressions of TNF-α and IFN-γ in the hesperidin group were significantly downregulated （P〈0. 01）. But there was no significant difference between hesperidin group and model control group in 6 h after treated with Con A（P〉0. 05）. Conclusion Hesperidin pretreatment protects mice from Con A-induced acute liver injury possibly by inhibiting the expression of TNF-α and IFN-γ in the liver of mice.