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目的探讨粒细胞集落刺激因子通过影响小胶质细胞的活化对缺氧导致的脑室周围白质损伤(PWMD)的保护作用。方法将1d龄新生小鼠108只随机分为对照组、损伤组及治疗组,后两组经缺氧箱缺氧法制备脑室周围白质损伤模型,造模前及造模后2h给予治疗组存活鼠腹腔注射粒细胞集落刺激因子,之后每日1次,1d、3d、7d后各处死3组部分动物。取全脑切片进行免疫荧光双标检测小胶质细胞的募集以及炎性因子的分泌情况;取脑室周围白质,采用酶联免疫吸附剂测定法检测炎性因子分泌水平;利用RT-PCR法检测致炎因子和抑炎因子的分泌以及两类活化小胶质细胞的数量和比例变化情况;治疗组结束给药于7d,分别于5d、8d、10d、12d、30d进行神经行为学实验,观察其感觉运动功能的发育。结果粒细胞集落刺激因子能够促进小鼠运动功能恢复,改善脑瘫症状,改变活化小胶质细胞中M1型细胞和M2型细胞的数量和比例,使促炎性因子分泌降低,抑炎因子及神经营养因子分泌升高,改善损伤导致的神经发育异常及神经行为缺陷。结论利用粒细胞集落刺激因子干预脑室周围白质损伤可以抗炎,并可以诱导小胶质细胞向神经保护方向转化,调节炎性因子和神经营养因子的分泌。
Objective To investigate the protective effect of granulocyte-colony stimulating factor (rhG-CSF) on periventricular white matter damage (PWMD) induced by hypoxia by affecting microglial activation. Methods One hundred and eighty one-day-old neonatal mice were randomly divided into control group, injury group and treatment group. The latter two groups were prepared by hypoxia-hypoxia hypoxic-ischemic model of periventricular white matter injury. Rats were injected intraperitoneally with granulocyte colony-stimulating factor, and then three groups of animals were sacrificed on day 1, day 3, day 7, respectively. Whole brain sections were taken to detect the recruitment of microglia and the secretion of inflammatory cytokines by double immunofluorescence staining. The white matter around the periventricular was measured. The secretion of inflammatory cytokines was detected by enzyme-linked immunosorbent assay (ELISA) The secretion of inflammatory cytokines and proinflammatory cytokines and the changes of the number and proportion of activated microglial cells in two groups were observed. The treatment group was given the drug for 7 days, and the neurobehavioral experiments were performed on the 5th, 8th, 10th, 12th and 30th days, respectively. It senses the development of motor function. Results Granulocyte colony-stimulating factor could promote the recovery of motor function, improve the symptoms of cerebral palsy, change the number and proportion of M1 type cells and M2 type cells in activated microglial cells, decrease the secretion of proinflammatory cytokines, inhibit the inflammatory factors and nerves Increased secretion of trophic factors, to improve the damage caused by neurodevelopmental abnormalities and neurological behavioral defects. Conclusion The use of granulocyte colony-stimulating factor in the periventricular white matter injury can be anti-inflammatory, and can induce microglia to neuroprotective direction, regulating the secretion of inflammatory cytokines and neurotrophic factors.