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小胶质细胞是中枢神经系统内的免疫细胞,当脑组织出现损伤时,小胶质细胞被激活,对脑组织起到保护作用。在自身免疫性脑脊髓炎模型大鼠和视神经脊髓炎患者体内,均观察到在脊髓炎性病灶及小胶质细胞内,P2X4受体表达上调。本课题组进行在体和离体实验,用LPS活化小胶质细胞,观察P2X4受体在小胶质细胞炎性反应中的作用。膜片钳检测显示,在LPS激活的小胶质细胞内,P2X4受体活性增加。P2X4受体阻断剂可显著降低小胶质细胞的膜皱缩、TNFα的分泌、细胞形态的改变及LPS导致的小胶质细胞死亡。在体研究显示,LPS髓内注射后会诱发炎性反应,迅速导致小胶质细胞丢失;给予P2X4受体阻断剂可显著减少小胶质细胞的丢失,而P2X4受体激活剂则可显著增加小胶质细胞的丢失。海马齿状回的小胶质细胞特别容易被LPS诱导的炎症反应激活。注射LPS后2 h,位于海马齿状回的小胶质细胞即被激活,大约24 h后死亡,P2X4受体阻断剂可减少LPS诱导的小胶质细胞活化和死亡。上述数据提示,P2X4受体对于小胶质细胞的激活和存活有重要的调控作用。
Microglia are immune cells in the central nervous system. When damage occurs in brain tissue, microglia are activated and play a protective role in brain tissue. In autoimmune encephalomyelitis model rats and optic neuromyelitis patients were observed in spinal cord inflammatory lesions and microglia, P2X4 receptor expression was up-regulated. Our group conducted in vitro and in vivo experiments, activated microglial cells with LPS to observe the role of P2X4 receptor in the microglial inflammatory response. Patch clamp testing showed increased P2X4 receptor activity in LPS-activated microglia. P2X4 receptor blocker can significantly reduce the membrane collapse of microglia, TNFα secretion, changes in cell morphology and microglia death caused by LPS. In vivo studies showed that intraperitoneal injection of LPS induced an inflammatory response and rapidly led to the loss of microglial cells. The administration of P2X4 receptor blockers significantly reduced the microglial loss, whereas the P2X4 receptor activator significantly increased Increase the loss of microglia. Microglia in the dentate gyrus of the hippocampus are particularly susceptible to activation by LPS-induced inflammation. At 2 h after injection of LPS, microglial cells located in the dentate gyrus of the hippocampus were activated and died after about 24 h. P2X4 receptor blockers reduced LPS-induced microglial activation and death. The above data suggest that P2X4 receptor plays an important regulatory role in microglial activation and survival.