【摘要】 目的探讨CD40L在阿尔茨海默病病理机制中的免疫调节作用及对神经元的影响。方法通过Aβ1-42寡聚体单独或联合CD40L干预原代小胶质细胞,检测细胞表面炎性介质的释放、抗原表达及炎性上清液对神经元的影响。结果Aβ1-42联合CD40L与Aβ1-42单独干预比较,小胶质细胞释放TNF-α明显增加(2869.35±63.47、1222.03±46.86,P<0.01);炎症上清培养神经元后,LDH漏出明显增加(104.43±4.12、57.90±3.20,P<0.01);细胞表面CD40及MHCⅡ分子共表达阳性率增高(30.2%、23.3%);加入抗CD40抗体后,细胞释放TNF-α明显减少(817.92±48.52、2869.35±63.47,P<0.01),神经元释放LDH减少(36.42±1.03、104.43±4.12,P<0.01),细胞表面CD40及MHCⅡ分子共表达阳性率下降(16.23%、30.2%)。结论CD40L可以促进Aβ1-42诱导的小胶质细胞活化,产生固有免疫及适应性免疫应答,加重神经元的损伤。更多还原

【Abstract】 Objectives To explore the potential role of CD40L in the immunological regulation in Alzheimer’ s disease.Methods Aβ1-42 oligomers alone or in combination with CD40L were used to treat primariy microglial cell.Following the treatment,the release of inflammatory mediators,antigen expression in cell surface and the effects of supernatant from microglia cultures on neurons were examined.Results Compared with Aβ1-42 alone,combination of CD40L and Aβ1-42 significantly increased the TNF-αrelease from microglia(2869.35 ± 63.47,1222.03 ± 46.86,P < 0.01).The supernatants from microglia cultures increased LDH level(104.43 ± 4.12,57.90 ± 3.20,P < 0.01) and induced co-expression of cellular surface CD40 and MHCⅡ(30.2% vs 23.3%) in neuronal cultures.In contrast,treatment with anti-CD40 antibody significantly attenuated Aβ1-42 and CD40-induced TNF-αrelease(817.92 ± 48.52,2869.35 ± 63.47,P < 0.01),LDH level(36.42 ± 1.03,104.43 ± 4.12,P < 0.01)and co-expression of CD40 and MHCⅡ(16.23%,30.2%) compared with non-treated cultures.Conclusion CD 40L can promote Aβ1-42-induced activation of microglia,increase immunoresponse,thereby inducing neuron injury.更多还原