莱菔硫烷对帕金森病大鼠脑内多巴胺能神经元的保护作用及机制

目的 观察莱菔硫烷(sulforaphane,SF)对帕金森(PD)病大鼠模型脑内黑质多巴胺能神经元的保护作用.方法 健康成年雄性Wistar大鼠背部皮下注射鱼藤酮制备PD大鼠模型,药物治疗组同时给予大鼠腹腔注射EGCG.采用分光光度法检测大鼠脑内丙二醛(MDA)和还原型谷胱甘肽(GSH),免疫细胞化学和免疫印记检测大鼠中脑黑质及纹状体中络氨酸羟化酶(TH)的表达变化.结果 Western blot结果显示试验组大鼠脑内中脑和纹状体中TH蛋白表达都比对照组有明显降低(P<0.05);莱菔硫烷药物干预后TH蛋白在中脑和纹状体比试验组明显增高(P<0.05),但是较对照组仍有明显减少(P<0.05).实验组大鼠在给予鱼藤酮背部皮下注射后导致大鼠脑内纹状体中脂质代谢产物MDA含量比对照组明显增加(P<0.01).莱菔硫烷药物干预组大鼠脑内纹状体中MDA明显减少(P<0.05),但较对照组仍明显增加(P<0.05).同时我们发现鱼藤酮背部皮下注射可以导致实验组大鼠脑内纹状体中GSH的含量比对照组明显减少(P<0.01);莱菔硫烷药物干预后大鼠脑内纹状体中GSH含量较实验组明显增加(P<0.05),但较对照组仍明显减少(P<0.05).结论 氧化应激在PD发病中起着非常重要的作用,抗氧化治疗能有效减轻大鼠脑内多巴胺能神经元损伤情况,同时改善PD样症状,为PD的治疗提供了新的靶点.

The protective effects of sulforaphane on dopaminergic neurons in brain substantia nigra of rats with Parkinson's disease and its action mechanism

Objective To investigate the protective effects of sulforaphane (SF) on dopaminergic neurons in brain substantia nigra of rats with Parkinson's disease (PD) induced by rotenone, and to explore its action mechanism.Methods The animal models with PD were established by back subcutaneous injection with rotenone in healthy adult male Wistar rats,at the same time, the rats in drug intervention group were given EGCG by intraperitoneal injection.Then the levels of malondialdehyde (MDA) and reduced glutathione (GSH) were detected by spectrophotometry,and the changes of levels of tyrosine hydroxylase (TH) in brain substantia nigra and striatum of rats were detected by immunocytochemistry and Westen Blot.Results The results by Western Blot showed that the expression levels of TH in midbrain and striatum of rats in experimental group were significantly decreased,as compared with those in control group (P<0.05),and which in drug intervention group were significantly higher than those in trial group (P<0.05),however, which were significantly lower than those in control group (P<0.05).The levels of MDA in trial group were obviously increased,as compared with those in control group (P<0.0),however,which in drug intervention group were significantly decreased,but which were still higher than those in control group (P<0.05),as compared with those in control group (P<0.05).Moreover the levels of GSH in brain striatum of rats in trial group were significantly lower than those in control group (P<0.01),which in drug intervention group were significantly increased,as compared with those in experimental group, but which were still lower than those in control group (P<0.05).Conclusion The oxidative stress plays an important role in the pathogenesis of PD,and anti-oxidation treatment can effectively relieve the injury of dopaminergic neurons in brain of rat,improve the symptoms of PD simultaneously,which provides an new target for treatment of PD.