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目的研究抗结核药物致肝损伤时沉默信息调节因子1(SIRT1)与CCAAT/增强子结合蛋白同源蛋白(CHOP)的关系及白藜芦醇对肝损伤的作用。方法雄性SD大鼠随机分为正常组、模型组(异烟肼+利福平各50mg·kg~(-1)·d~(-1))、实验组(模型组基础上+白藜芦醇15 mg·kg~(-1)·d~(-1))、对照组(利福平50 mg·kg~(-1)·d~(-1)),每组8只。3周后处死大鼠,检测血清肝生化指标、肝组织超氧化物歧化酶(SOD)、丙二醛(MDA)、观察肝病理学变化,免疫印迹法检测肝SIRT1和CHOP表达水平。结果与模型组比,白藜芦醇显著改善血清肝生化指标,降低MDA含量[(1.76±0.32)vs(2.23±0.36)nmol·mg prot(-1)]、增加SOD活性[(85.33±11.52)vs(67.36±12.19)U·mg prot(-1)](均P<0.05),改善肝病理损伤,增加SIRT1表达,减少CHOP表达。结论白藜芦醇改善大鼠肝损伤,可能与其激活SIRT1、减轻氧化应激及抑制CHOP表达有关。
Objective To study the relationship between SIRT1 and CCAAT / enhancer binding protein homologous protein (CHOP) induced by anti-TB drugs in liver injury and the effect of resveratrol on liver injury. Methods Male Sprague-Dawley rats were randomly divided into normal group, model group (isoniazid + rifampicin 50 mg · kg -1 · d -1), experimental group (model group + Alcohol 15 mg · kg -1 · d -1 and control group 50 mg · kg -1 · d -1, 8 in each group. After 3 weeks, the rats were sacrificed and the serum liver biochemical indexes, liver tissue superoxide dismutase (SOD) and malondialdehyde (MDA) were measured. The pathological changes of liver were observed. The expressions of SIRT1 and CHOP in liver were detected by Western blotting. Results Compared with the model group, resveratrol significantly improved serum liver biochemical parameters and decreased the content of MDA [(1.76 ± 0.32) vs (2.23 ± 0.36) nmol · mg prot (-1)], and increased the activity of SOD [(85.33 ± 11.52 ) vs (67.36 ± 12.19) U · mg prot (-1)] (all P <0.05), improve liver pathology, increase SIRT1 expression and decrease CHOP expression. Conclusion Resveratrol can improve liver injury in rats, which may be related to its activation of SIRT1, reduction of oxidative stress and inhibition of CHOP expression.