牛磺酸和环孢素A对氯化锰致大鼠肝脏线粒体氧化损伤作用的影响

    Effect of taurine and cyclosporine A on oxidative damage of liver mitochondrial induced by manganese chloride in rats

    • 摘要: 目的:观察牛磺酸(taurine,Tau)和环孢素A(cyclosporine A,CSA)对锰(Mn)致大鼠肝脏线粒体氧化损伤作用的影响,并探讨Mn致肝脏毒性的细胞分子学机制。方法:24只雄性SD大鼠按体重随机均分为4组。第1组为对照组,皮下注射生理盐水;第2组为单纯染Mn(MnCl2)组,皮下注射生理盐水;第3、4组为预处理(Tau+MnCl2组和CSA+MnCl2组),分别皮下注射Tau(100 mg/kg)和CSA(1 mg/kg)。皮下注射2 h后,第1组腹腔注射生理盐水,第2~4组腹腔注射MnCl2溶液(32 mg/kg),染Mn 30天,Tau和CSA隔日注射1次,共干预15次。最后1次染Mn后24 h,切取肝组织。测定肝线粒体膜肿胀度、膜电位、PT孔和SDH活性、细胞色素C含量以及GSH-PX活性、OH.含量。结果:大鼠单纯染Mn 30天后,与对照组比较线粒体膜肿胀度光密度降低(P<0.05),PT孔、线粒体膜电位光密度降低,GSH-PX和SDH活性降低,细胞色素C和OH.含量升高(P<0.05~P<0.01);Tau+MnCl2组与MnCl2组相比,线粒体膜肿胀度光密度、PT孔、线粒体膜电位光密度升高(P<0.05~P<0.01),GSH-PX和SDH活性升高,细胞色素C和OH.含量降低(P<0.01);CSA+MnCl2组与MnCl2组相比,PT孔、线粒体膜电位光密度升高,GSH-PX和SDH活性升高,细胞色素C含量降低(P<0.01)。结论:Tau和CSA对Mn引起的肝脏线粒体氧化损伤有不同程度的拮抗作用。

       

      Abstract: Objective: To study the effect of different doses of manganese (Mn) on oxidative damage of liver mitochondrial induced by Mn chloride,and to explore the cell molecular mechanism of Mn-induced exeitotoxicity.Methods: Twenty four male SD rats were randomly divided into four groups by weight.The first group (control group) were given subcutaneous injection of physiological saline only;the second group (Mn-exposed group) were injected 32 mg/kg of MnCl2 subcutaneously;the third and fourth groups were intraperitoneally injected 100 mg/kg of taurine (Tau) and 1 mg/kg of cyclosporine A (CSA),respectively.Two hours after subcutaneous injection,the first group were intraperitoneally injected physiological saline,and the other three groups received intraperitoneal injection of 32 mg/kg of MnCl2 for 30 days,and Tau and CSA were injected every other day for 15 times.At the 24th hour after the last administration of MnCl2,the rats were killed and the liver was taken to detect the mitochondrial swelling amplitude,mitochondrial membrane potential (MMP),permeability transition pore (PT pore),the activity of GSH-PX,SDH and the content of cytochrome C and OH·.Results: Compared with control group,the mitochondrial swelling amplitude,PT pore,MMP,the activity of GSH-PX and SDH decreased in the MnCl2 group,while the content of cytochrome C and OH·increased (P<0.05 to P<0.01).Compared with MnCl2 group,the mitochondrial swelling amplitude,PT pore and MMP increased in Tau pretreatment group (P<0.05 to P<0.01),while the activity of GSH-PX and SDH increased,and the content of cytochrome C and OH·decreased (P<0.01).Compared with control group,the activity of GSH-PX and SDH,PT pore and MMP increased in CSA pretreatment group,while the content of cytochrome C decreased (P<0.01).Conclusions: Tau and CSA have some antagonistic effects on oxidative damage of liver mitochondrial induced by manganese.

       

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