目的观察磷脂酰肌醇3激酶(PI3K)/蛋白激酶B (Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路相关蛋白在帕金森病模型大鼠黑质区的表达及变化情况。方法96只健康Sprague-Dawley大鼠随机分为假手术组、模型组、PI3K抑制剂LY294002组及p-mTOR抑制剂雷帕霉素组,每组又分为模型制备成功后4 d和8 d两个亚组,每个亚组12只。后三组颈背部皮下注射鱼藤酮制作帕金森病大鼠模型,相应时间点免疫组化及Western blotting检测大鼠黑质区PI3K、p-Akt、p-mTOR蛋白表达。结果与假手术组比较,模型组各时间点PI3K、p-Akt和p-mTOR蛋白表达增加(P<0.05),8 d亚组高于4 d亚组(P<0.05)。与模型组比较,LY294002组各时间点p-Akt、p-mTOR蛋白表达减少(P<0.05),PI3K蛋白表达无明显变化(P>0.05);雷帕霉素组各时间点p-mTOR蛋白表达下降(P<0.05),PI3K、p-Akt蛋白表达无明显变化(P>0.05)。结论黑质PI3K/Akt/mTOR信号通路激活可能是帕金森病发生、发展的重要机制之一。
ObjectiveTo observe the expression of phosphatidylinositol 3-kinase (PI3K) / protein kinase B (Akt) / mammalian target of rapamycin (mTOR) signaling pathway in substantia nigra in rats with Parkinson's disease (PD). MethodsA total of 96 Sprague-Dawley rats were randomly divided into sham group, model group, PI3K inhibitor LY294002 group and mTOR inhibitor rapamycin group. Each group was divided into 4 days and 8 days subgroups after the model. PD model was established by injecting rotenone subcutaneously. The expression of PI3K, p-Akt and p-mTOR in substantia nigra was detected with immunohistochemistry and Western blotting. ResultsCompared with the sham group, the expression of PI3K, p-Akt and p-mTOR increased in the model group (P<0.05), and was more in 8 days subgroup than in 4 days subgroup (P<0.05). Compared with the model group, the expression of p-Akt and p-mTOR reduced in the LY294002 group (P<0.05), while the expression of PI3K varied little (P>0.05); the expression of p-mTOR decreased in the rapamycin group (P<0.05), while the expression of PI3K and p-Akt varied little (P>0.05). ConclusionPI3K/Akt/mTOR signaling pathway is over activated in substantia nigra in rats with Parkinson's disease, which may play an important role in occurrence and development of the disease.
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