趋化因子CC配基2对α?Synuclein诱导的小胶质细胞增殖及神经元凋亡的影响Study on the effect of CCL2 on the proliferation of microglia and apoptosis of Neuron induced byα-Synuclein
张黎军,赵盼盼,赵建华,王超伟,李青,随瑞斌,袁彬
摘要(Abstract):
目的探讨趋化因子CC配基2(CCL2)对α?突触核蛋白(α?Synuclein)介导的小胶质细胞增殖及神经元凋亡的影响。方法体外分离培养原代小胶质细胞和原代神经元。小胶质细胞分为4组,依次为对照组、CCL2组、α?Synuclein组、CCL2+α?Synuclein组。对照组中加入等量的PBS,CCL2组细胞中加入含有CCL2浓度为0.05ng/μL的培养液。α?Synuclein组细胞中加入含有α?Synuclein浓度为0.2ng/μL的培养液。CCL2+α?Synuclein组中加入含有0.05ng/μL CCL2、0.2ng/μLα?Synuclein的细胞培养液。培养24h后,检测小胶质细胞增殖情况及细胞中α?Synuclein蛋白水平,同时检测细胞培养液中TNF-α、IL-1β、NO含量。用各组小胶质细胞培养液培养原代神经元,观察神经元凋亡情况及神经元中Cleaved Caspase-3、Akt、p-Akt水平。结果 CCL2组、α?Synuclein组、CCL2+α?Synuclein组小胶质细胞增殖活性及分泌TNF-α、IL-1β、NO水平明显高于对照组(P<0.05)。CCL2组、CCL2+α?Synuclein组小胶质细胞中α?Synuclein水平明显高于对照组(P<0.01)。CCL2组、α?Synuclein组、CCL2+α?Synuclein组小胶质细胞培养液作用后的神经元凋亡率及Cleaved Caspase-3蛋白水平明显高于对照组,pAkt水平低于对照组(P<0.01)。结论 CCL2促进α?Synuclein引起的小胶质细胞增殖和分泌TNF-α、IL-1β、NO的能力,对α?Synuclein引起的神经元凋亡也具有促进作用,促凋亡作用机制可能与Akt信号通路有关。
关键词(KeyWords): 小胶质细胞;神经元;CCL2;凋亡;信号通路;小鼠
基金项目(Foundation): 河南省科技厅科技攻关项目,编号:172102310685
作者(Author): 张黎军,赵盼盼,赵建华,王超伟,李青,随瑞斌,袁彬
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