趋化因子mRNA在多发性硬化中的表达

Chemokine mRNA Expression in Patients with Multiple Sclerosis

目的 本研究观察了多发性硬化 ( MS)患者趋化因子 m RNA在周围血及 CSF中的表达。方法 采取MS患者外周血及 CSF,以其他非炎性神经系统疾病 ( OND)及健康人 ( HC)为对照组 ,分离单个核细胞 ( MNC) ,在完全培基中与自身抗原 MBP、对照抗原 ACh R培养 ,3d后收集细胞 ,涂片 ,用地高辛标记的寡核苷酸探针进行原位杂交 ( ISH) ,检测 C-C趋化因子单核细胞炎性蛋白 -1α/β( MIP-1α/β)、单核细胞趋化蛋白 ( MCP-1 )及正常T细胞表达及分泌的调节活化因子 ( RANTES) m RNA的表达。结果 MS患者外周血中 MIP-1 α/ β、MCP-1及RANTES m RNA阳性细胞表达 ,与 OND组及 HC组相比明显增高 ,差异显著 ;MS患者 CSF中 MNC的 MIP-1α及 RANTES m RNA高于 OND组 ,差异有显著性 ;MS急性期外周血中 MBP刺激的 MIP-1α m RNA与 MS缓解期相比差异不明显 ,而急性期 MBP刺激的 MCP-1 m RNA阳性细胞数多于其缓解期 ;MS患者急性期 CSF内 RANTES m RNA阳性细胞数高于缓解期。结论 趋化因子可能参与 MS的发病 ,与炎性细胞进入 CNS有关 ;RANTES及 MCP-1与 MS的缓解 -复发有关。

Objective In this study, we demonstrated the chemokine mRNA expression in blood and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS).Methods We have isolated blood mononuclear cell(MNC) by density gradient centrifugation of heparinized whole blood and CSF MNC from 39 MS patients. MNC were cultured 72 hour with MBP,AChR, without antigen. Detection of mRNA for monocyte chemoattractant protein 1(MCP 1),macrophage inflammatory protein 1α/β(MIP 1α/β)with regulated activation,normal T cell and secreted(RANTES)mRNA expressions were performed by in situ hybridization (ISH).Results Numbers of blood MNC expressing MIP 1α, MCP 1 and RANTES mRNA were much higher in patients with MS than OND and HC; Numbers of CSF MNC expressing MIP 1α and RANTES mRNA were much higher in patients with MS than OND and HC. In patients with MS, the mean numbers of MIP 1α and RANTES mRNA positive cells were about 5 fold higher in CSF compared with that in blood.MS patients examined during clinical exacerbations had higher numbers of MBP reactive MCP 1 mRNA positive cells in blood and spontaneously RANTES mRNA expressing cells was higher in CSF compared with patients examined during remission. Conclusions Chemokine might play a role in the inflammation of MS. MCP 1 mRNA positive cells in blood and RANTES mRNA expressing cells in CSF were associated with clinical variables of MS.