1,2-二甲基-3-羟基-4-吡啶酮和牛磺酸联合应用对铝染毒大鼠肾功能及抗氧化系统的保护作用

Protective effect of deferipone and taurine in combination on antioxidant system, ATPase and function in kidneys of rats exposed to aluminum

目的探讨1,2-二甲基-3-羟基-4-吡啶酮(deferipone,DFP)和牛磺酸联合作用对染铝大鼠肾脏功能、抗氧化系统及ATP酶活力的影响。方法将56只SPF级雄性Wistar大鼠按体重随机分为7组,以灌胃方式染毒。其中,阴性对照组给予1.0 ml/d生理盐水,连续8周。前4周,铝染毒组、牛磺酸干预组、低剂量DFP干预组、高剂量DFP干预组、牛磺酸与低剂量DFP联用组、牛磺酸与高剂量DFP联用组均给予281.40 mg/(kg·d)AlCl_3·6H_2O;后4周,各组分别给予1.0 ml/d生理盐水、400 mg/(kg·d)牛磺酸、13.82 mg/(kg·d)DFP、27.44 mg/(kg·d)DFP、400 mg/(kg·d)牛磺酸+13.82 mg/(kg·d)DFP、400 mg/(kg·d)牛磺酸+27.44 mg/(kg·d)DFP。测定大鼠肾脏Na^+K^+-ATP酶、Mg^(2+)-ATP酶、Ca^(2+)-ATP酶、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力和丙二醛(MDA)含量及肌酐(Cr)、尿素氮(BUN)含量。结果与铝染毒组相比,各干预组大鼠肾脏GSH-Px、Na^+K^+-ATP酶、Mg^(2+)-ATP酶活力均明显升高,肾脏MDA含量和血清BUN含量均明显降低,差异有统计学意义(P<0.05);且高剂量DFP干预组及联合用药组大鼠肾脏SOD活力明显升高,差异有统计学意义(P<0.05)。与单独用药组相比,联合用药组Na^+K^+-ATP酶、Mg^(2+)-ATP酶、SOD、GSH-Px活力明显升高,MDA和血清BUN含量明显降低,差异有统计学意义(P<0.05)。各组间Ca^(2+)-ATP酶活力及血清Cr含量无明显差异(P>0.05)。结论在一定剂量范围内,与牛磺酸或DFP单独用药相比,牛磺酸和DFP联合用药可以对染铝大鼠肾脏功能及抗氧化系统起到更好的保护作用。

Objective To understand the protective effect of 1,2-dimethyl-3-hydroxy-4-pyridone （deferipone, DFP） and taurine （Tau） in combination on antioxidant system, ATPase and function in kidneys of rats exposed to aluminum. Methods A total of 56 male Wistar rats of SPF level were randomized into seven groups according to the weight. The tested agents were given through gavage. The rats in control group received 1.0 ml/d normal saline for eight weeks. A1 exposure groups, Tau groups, low-dose DFP groups, hlgh-dose DFP groups, Tau and low-dose DFP groups, Tau and high-dose DFP groups received 281.4 mg/kg daily aluminum chloride hexahydrate （A1C13＂6H20） for the first four weeks. Then, they received 1.0 ml/d normal saline, 400 mg/（kg-d） Tau, 13.82 mg/（kg.d） DFP, 27.44 mg/（kg.d） DFP, 400 mg/（kg.d） Tau ＋13.82 mg/（kg.d） DFP, 400 mg/（kg＇d） Tau ＋27.44 mg/（kg-d） DFP, respectively. The content of MDA, Cr, BUN and the activities of Na^＋K^＋-ATPase, Mg2＋-ATPase, Ca^2＋-ATPase, SOD and GSH-Px were determined. Results Compared with A1 exposure group, the activities of Na^＋K^＋-ATPase, Mg^2＋-ATPase, SOD and GSH-Px were significantly higher （P〈O.05）, the MDA and BUN contents were significantly lower （P〈O.05） in all treatment groups, and the activity of SOD was significantly higher （P〈0.05） in high-dose DFP group and DFP combined with taurine groups. Compared with group of sole medication, the activities of Na^＋ K＋-ATPase, Mg2＋-ATPase, SOD and GSH-Px were significantly higher （P〈0.05） and the MDA, BUN contents were significantly lower （/9〈0.05） in DFP and taurine in combined groups. There was no significant change on activity of Ca^2＋-ATPase and content of Cr in different groups. Conclusion Single use of DFP and Tau may protect the antioxidant system and ATPase, but DFP and Tau in combination at an appropriate dose may present a better protective effect in comoarison to monotheraov.