SH-SYSH-SY5Y与UU87细胞共培养条件性培养基可降低N-甲基-salsolinol介导THP-THP-1细胞的凋亡

Attenuation of N-methyl-salsolinol mediated apoptosis of THP-1 cells by the conditioned medium from co-cultures of SH-SY5Y and U87 cells

神经免疫在帕金森病(PD)的致病机理中发挥重要的作用,PD患者的外周血淋巴细胞的数量发生了变化,提示外周免疫系统在PD的发生发展中发挥一定的作用。但是外周单核细胞(PBMC)在其中发挥的具体作用尚不清楚。外源性神经毒素(MPTP)类似物,内源性神经毒素(NMSal)可能是导致PD发生的一种因素。研究采用NMSal损伤的SH-SY5Y与U87细胞共培养的条件性培养基培养外周单核细胞THP-1,探讨NMSal损伤的多巴胺能神经元细胞对外周单核细胞的影响。结果表明,该条件性培养基可以降低NMSal毒性诱导的THP-1细胞的凋亡、氧化应激水平(MDA和H2O2)、线粒体的损伤和凋亡相关蛋白FADD、Bax和caspase3的表达和活化水平。PD病人中损伤的多巴胺能神经元与星形胶质细胞的相互作用可能会影响PBMC,进而影响PD病情的进展。

Neuroinflammation has been implicated in the pathogenesis of neurodegenerative Parkinson＇s disease （PD）. Moreover, some studies have found that total T cell pool was changed in PD. However, little is known about peripheral blood mononuclear cells （PBMC） in the pathogenesis of PD. Recent studies have demonstrated that endogenous neurotoxin 1,2（N）- dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline （N-methyl-salsolinol, NMSal）, an analogue of 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine （MPTP） in the brain, could induce degeneration of dopaminergic neurons and cause neuroimmune dysfunction in PD. In the present study, we examined the effect of conditioned medium from NMSal treated co-cultures of neuroblastoma SH-SY5Y cells and glioma cell line U87 cells on human monocyte THP-1 ceils. The results showed that the conditioned medium attenuated apoptosis of THP-1 ceils mediated by NMSal. The conditioned medium inhibited the swelling and rupture of mitochondrial membrane, reduced the production of malondialdehyde （MDA） and H202, and decreased expression levels of caspase3, Bax and FADD of THP-1 cells induced by NMSal. These indicated that the interaction of neurons with astrocyte could affect cell amount and immune function of PBMC, then affecting the progression of PD.