1,2-二甲基-3-羟基-4-吡啶酮和牛磺酸联合干预对铝染毒大鼠大脑皮层抗氧化系统的保护作用

Protective effects of 1,2-dimethyl-3-hydroxy-4-pyridone combined with taurine on antioxidant system in cortex 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大脑皮层抗氧化系统的影响。方法将70只健康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 ml生理盐水,连续8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+低剂量DFP干预组和牛磺酸+高剂量DFP干预组在前4周分别给予281.40 mg/kg三氯化铝溶液,后4周分别给予1 ml生理盐水、400 mg/kg牛磺酸、13.82 mg/kg DFP、27.44 mg/kg DFP、400 mg/kg牛磺酸、400 mg/kg牛磺酸;牛磺酸+低剂量DFP干预组和牛磺酸+高剂量DFP干预组给予400 mg/kg牛磺酸6 h后分别给予13.82、27.44 mg/kg DFP,每天1次。测定大鼠大脑皮层SOD、GSH-Px活力和MDA含量。结果与阴性对照组比较,铝染毒组大鼠大脑皮层SOD和GSH-Px活力均较低,而MDA含量较高,差异有统计学意义(P<0.05)。与铝染毒组相比,在单独干预组中,仅高剂量DFP干预组可以显著提高SOD和GSH-Px活力,降低MDA的含量;牛磺酸干预组可以显著提高GSH-Px的活力水平以及降低MDA含量。在DFP和牛磺酸的联合作用下,大鼠大脑皮层的SOD和GSH-Px活力水平以及MDA含量均基本恢复正常。其中,与牛磺酸干预组和低剂量DFP干预组比较,牛磺酸+DFP干预组可以显著提高SOD和GSH-Px活力,降低MDA含量;且以牛磺酸+低剂量DFP干预组尤为显著。结论在本实验剂量范围内,牛磺酸和DFP联合干预可以对染铝大鼠大脑皮层的抗氧化系统起到保护作用,且效果优于牛磺酸或DFP单独干预。

Objective To know the effects of 1,2-dimethyl-3-hydroxy-4-pyridone（DFP） combined with taurine on anti-oxidant system in the cortex of rats exposed to aluminum. Methods Seventy healthy male Wistar rats of SPF grade were randomly divided into seven groups according to their weight. The tested chemicals were given by gavage,once a day, the control group received 1.0 ml/d saline. Aluminum exposure group,taurine does group,DFP low dose group,DFP high dose group,taurine ＋DFP low dose group,taurine ＋DFP high dose group received 281.4 mg/kg body weight daily Al Cl3 for the first four weeks. Then for the last four weeks,they were given 1.0 ml/d saline,400 mg/kg body weight taurine,13.82 mg/kg DFP,27.44 mg/kg DFP,400 mg/kg taurine,400 mg/kg taurine,respectively; Taurine＋DFP low dose group and taurine＋DFP high dose group were given 13.82,27.44 mg/kg DFP 6 h right after the taurine treatment, respectively. The content of malondialdehyde（MDA）,the activities of superoxide dismutase（SOD） and glutathione peroxidase（GSH-Px） in the cortex of rats were determined.Results Aluminum intake caused significant increase of MDA but reduction of the activities of SOD and GSH-Px compared with control group（P〈0.05）. Compared with aluminum exposure group,in groups of sole medication only administration of high dose DFP significantly reduced MDA content, and improved the activities of SOD and GSH-Px（P〈0.05）;The activities of GSH-Px were significantly higher（P〈0.05） and the MDA content were significantly lower（P〈0.05） in taurine does group. The content of MDA,the activities of SOD and GSH-Px almost recovered to normal with administration of taurine combined with DFP. Compared with group of sole medication,the activities of SOD and GSH-Px were significantly higher（P〈0.05） and the MDA content were significantly lower（P〈0.05） in DFP and taurine combined medication groups; Taurine＋DFP low dose group was especially significant（P〈0.05）. Conclusion At the dose in the present study,DFP combined with taurine may protect the antioxidant system in cortex of rats exposed to aluminum and it is prior to DFP or taurine in single use.