mTOR信号通路的激活在左旋多巴诱发异动症中的作用及机制研究(1)
【摘要】 目的：探討mTOR信号通路的激活在左旋多巴诱发异动症(L-dopa induced dyskinesia，LID)中的作用及可能机制。方法：60只普通雄性大鼠，其中选取10只作为健康对照组，皮下注射安慰剂葵花油2 mg/kg；其余50只采用鱼藤酮2 mg/kg，颈背部注射，以大鼠行为变化2～6分选为PD组；PD组大鼠L-dopa 10 mg+Benserazide诱导，制备LID模型，最终大鼠模型对照组(n=10)，PD组(n=10)，LID组(n=14)。Western Blot技术检测大鼠纹状体S6K的Thr389、S6Ser240/244表达及mTOR的蛋白活性(p70S6K)及免疫组织化学检测AMPA受体亚基GluR1、GluR2水平。结果：LID组大鼠Thr389、S6Ser240/244、代表mTOR蛋白活性p70S6K表达及GluR1、GluR2阳性细胞数均明显高于PD组及对照组，差异均有统计学意义(P<0.05)；PD组大鼠Thr389、S6Ser240/244、代表mTOR蛋白活性p70S6K表达及GluR1、GluR2阳性细胞数均明显高于对照组，差异均有统计学意义(P<0.05)。结论：mTOR信号通路激活参与了PD及LID的发病，mTOR信号通路激活Thr389位点，进而激活S6K，引发S6Ser240/244激活，导致PD、LID的发生及进展。而且mTOR激活后，AMPA受体亚基GluR1、GluR2功能增强，对LID的发生也具有促进作用。
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【关键词】 mTOR； 帕金森； 左旋多巴； 异动症； S6K； AMPA
【Abstract】 Objective：To explore the role and possible mechanism of activation of mTOR signaling pathway in Levodopa induced dyskinesia. Method：A total of 60 normal male rats，10 of them were selected as healthy control group and subcutaneously injected with placebo sunflower oil for 2 mg/kg.The other 50 rats were injected rotenone 2 mg/kg and neck back injection，and PD group was selected for 2-6 points of rat behavior change. PD group rats were induced by L-dopa 10 mg+Benserazide，and LID model was prepared.Finally，rat model control group (n=10)，PD group (n=10)，LID group.The Thr389 and S6Ser240/244 expression of S6K in the striatum and the protein activity of mTOR (p70S6K) were detected by Western Blot technique，the level of AMPA receptor subunit GluR1 and GluR2 were detected by immunohistochemistry.Result：The expression of Thr389， S6Ser240/244，P70S6K representing the activity of mTOR protein and the positive cells numbers of GluR1 and GluR2 in LID group were significantly higher than those in PD and control group，the differences were statistically significant (P<0.05).The expression of Thr389， S6Ser240/244，P70S6K representing the activity of mTOR protein and the positive cells numbers of GluR1 and GluR2 in PD group were significantly higher than those in control group，the differences were statistically significant (P<0.05).Conclusion：The activation of mTOR signaling pathway is involved in the pathogenesis of PD and LID.The mTOR signaling pathway activates the Thr389 site，then activates S6K，triggering the activation of S6Ser240/244，leading to the occurrence and development of PD and LID.After mTOR activation，the function of AMPA receptor subunit GluR1 and GluR2 were increased，which also promoted the occurrence of LID.
【Key words】 mTOR； Parkinson； Levodopa； Dyskinesia； S6K； AMPA, 百拇医药(柳学勇 陈小武)
, http://www.100md.com
【关键词】 mTOR； 帕金森； 左旋多巴； 异动症； S6K； AMPA
【Abstract】 Objective：To explore the role and possible mechanism of activation of mTOR signaling pathway in Levodopa induced dyskinesia. Method：A total of 60 normal male rats，10 of them were selected as healthy control group and subcutaneously injected with placebo sunflower oil for 2 mg/kg.The other 50 rats were injected rotenone 2 mg/kg and neck back injection，and PD group was selected for 2-6 points of rat behavior change. PD group rats were induced by L-dopa 10 mg+Benserazide，and LID model was prepared.Finally，rat model control group (n=10)，PD group (n=10)，LID group.The Thr389 and S6Ser240/244 expression of S6K in the striatum and the protein activity of mTOR (p70S6K) were detected by Western Blot technique，the level of AMPA receptor subunit GluR1 and GluR2 were detected by immunohistochemistry.Result：The expression of Thr389， S6Ser240/244，P70S6K representing the activity of mTOR protein and the positive cells numbers of GluR1 and GluR2 in LID group were significantly higher than those in PD and control group，the differences were statistically significant (P<0.05).The expression of Thr389， S6Ser240/244，P70S6K representing the activity of mTOR protein and the positive cells numbers of GluR1 and GluR2 in PD group were significantly higher than those in control group，the differences were statistically significant (P<0.05).Conclusion：The activation of mTOR signaling pathway is involved in the pathogenesis of PD and LID.The mTOR signaling pathway activates the Thr389 site，then activates S6K，triggering the activation of S6Ser240/244，leading to the occurrence and development of PD and LID.After mTOR activation，the function of AMPA receptor subunit GluR1 and GluR2 were increased，which also promoted the occurrence of LID.
【Key words】 mTOR； Parkinson； Levodopa； Dyskinesia； S6K； AMPA, 百拇医药(柳学勇 陈小武)