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目的探讨氧化应激作用下组蛋白去乙酰化酶2(histone deacetylase2,HDAC2)参与到异烟肼致大鼠肝损伤的可能机制。方法 SD大鼠56只,雌雄各半,随机分为实验组48只和对照组8只,实验组予以异烟肼55 mg/kg·bw连续灌胃3、7、10、14、21和28 d,对照组给予等容积蒸馏水灌胃。心脏取血检测ALT、AST变化,肝脏组织检测HDAC2、SOD、MDA、IL-8和TNF-α表达水平。结果连续给药后大鼠血清ALT、AST明显高于对照(F=27.02,F=8.37,均P<0.01);肝组织中总SOD活力呈下降趋势(F=11.15,P<0.01),在28d最低;MDA含量在14d后处于高水平状态(F=7.42,P<0.01);HDAC2蛋白表达量呈上升趋势,且差异具有统计学意义(F=58.34,P<0.01);IL-8、TNF-α总体上调,趋势基本一致(F=40.23,F=41.562,均P<0.01)。相关性分析结果表明:HDAC2与IL-8、TNF-α、MDA呈正相关(r=0.74;r=0.75;r=0.700,均P<0.01),与SOD呈负相关(r=-0.53,P<0.01)。结论异烟肼引发的氧化还原反应导致HDAC2上调,提示HDAC2可能参与异烟肼致大鼠肝损伤过程中,但作用程度还需进一步证明。
Objective To investigate the possible mechanism of oxidative stress-induced histone deacetylase 2 (HDAC2) involved in liver injury induced by isoniazid in rats. Methods Fifty-six SD rats were randomly divided into experimental group (n = 48) and control group (n = 8). The experimental group was treated with isoniazid 55 mg / kg · bw for 3, 7, 10, 14, 21 and 28 d, the control group given equal volume of distilled water gavage. Blood samples were taken from the heart to detect the changes of ALT and AST, and to detect the expression of HDAC2, SOD, MDA, IL-8 and TNF-α in liver tissues. Results The serum levels of ALT and AST in the serum of rats were significantly higher than those of the control group (F = 27.02, F = 8.37, all P <0.01) (F = 58.34, P <0.01). The levels of IL-8, The overall up-regulation of TNF-α showed the same trends (F = 40.23, F = 41.562, all P <0.01). Correlation analysis showed that there was a positive correlation between HDAC2 and IL-8, TNF-α and MDA (r = 0.74; r = 0.75; r = 0.700, all P <0.01) <0.01). Conclusion Isoniazid-induced redox reaction leads to HDAC2 upregulation, suggesting that HDAC2 may be involved in isoniazid-induced liver injury in rats, but the extent of the role needs further evidence.