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目的探讨Nrf2和HO-1在锰所致纹状体氧化应激中的作用及褪黑素(MT)对其的影响。方法小鼠82只,均分为6组,分别为对照组、低MnCl2组、中MnCl2组、高MnCl2组、MT对照组和MT+高MnCl2组。第5、6组提前皮下注射(sc)给予5 mg/kg MT,2 h后,第2、3、4和6组分别腹腔注射给予12.5、25、50和50 mg/kg MnCl2,连续2周。用流式细胞仪测定细胞内ROS,比色法检测GSH和MDA含量,免疫组化法检测Nrf2和HO-1表达,Western blotting检测Nrf2和HO-1的蛋白水平。结果与对照组相比,在各MnCl2组中ROS含量、MDA含量、Nrf2和HO-1的阳性表达及其蛋白水平均增加,GSH含量下降。而MT对照组中仅Nrf2和HO-1表达及蛋白水平均明显增加。与高MnCl2组相比,在MT+高MnCl2组ROS和MDA含量均明显下降,GSH含量、Nrf2和HO-1阳性表达及蛋白水平明显增加。结论褪黑素可拮抗锰所致的小鼠纹状体氧化应激,其机制可能与Nrf2和HO-1有关。
Objective To investigate the role of Nrf2 and HO-1 in the oxidative stress of striatum induced by manganese and the effect of melatonin (MT) on it. Methods Totally 82 mice were randomly divided into 6 groups: control group, low MnCl2 group, medium MnCl2 group, high MnCl2 group, MT control group and MT + high MnCl2 group. Groups 5 and 6 received 5 mg / kg MT sc in advance. After 2 hours, groups 2, 3, 4 and 6 received intraperitoneal injections of 12.5, 25, 50 and 50 mg / kg MnCl2 for 2 weeks . The intracellular ROS was measured by flow cytometry. The levels of GSH and MDA were detected by colorimetric assay. The expressions of Nrf2 and HO-1 were detected by immunohistochemistry. The protein levels of Nrf2 and HO-1 were detected by Western blotting. Results Compared with the control group, the content of ROS, MDA, the expression of Nrf2 and HO-1 and the protein level of MnCl2 increased, and the content of GSH decreased. While only the expression of Nrf2 and HO-1 in MT control group and protein levels were significantly increased. Compared with the high MnCl2 group, the content of ROS and MDA in the MT + high MnCl2 group decreased significantly, the content of GSH, the positive expression of Nrf2 and HO-1 and the protein level increased obviously. Conclusion Melatonin can antagonize manganese-induced oxidative stress in striatum of mice and its mechanism may be related to Nrf2 and HO-1.