神经生长因子对大鼠尾状核脑出血后脑组织炎症反应和神经元凋亡的影响

Effect of Nerve Growth Factor on Inflammation and Neuronal Apoptosis After Caudate Nucleus Intracerebral Hemorrhage in Rats

目的探讨鼠神经生长因子(nerve growth factor,NGF)对大鼠尾状核脑出血后脑组织炎症反应、神经元凋亡及白细胞介素-6(interleukin-6,IL-6)、细胞因子信号传导抑制因子-3(suppressor of cytokine signaling-3,SOCS-3)的影响。方法选择60只经非肝素化自体鼠尾血注入法建立的尾状核脑出血模型SD大鼠作为研究对象,随机分为假手术组、模型组和NGF组,各20只。分别于术后第1、3、5天观察血肿周围脑组织炎症反应、神经元凋亡情况,并采用免疫组织化学染色法检测血肿周围脑组织IL-6和SOCS-3表达情况。结果假手术组大鼠术后3个时间点血肿周围脑组织含水量比较无显著差异(P>0.05);模型组和NGF组大鼠术后各时间点血肿周围脑组织含水量均显著高于假手术组(P<0.05),NGF组大鼠术后各时间点血肿周围脑组织含水数量均显著低于模型组(P<0.05)。NGF组各时间点血肿周围脑组织炎症、水肿程度、神经元细胞坏死程度均显著好于模型组。模型组和NGF组大鼠术后各时间点血肿周围脑组织神经元细胞TUNEL染色阳性率、IL-6和SOCS-3染色阳性数目均显著高于假手术组(P<0.05);NGF组大鼠术后各时间点血肿周围脑组织神经元细胞TUNEL染色阳性率和IL-6染色阳性细胞数目均显著低于模型组(P<0.05),但SOCS-3染色阳性细胞数目显著高于假手术组(P<0.05)。结论NGF可能通过上调SOCS-3表达,下调IL-6表达改善脑出血后脑组织炎症反应、减少神经元凋亡等途径发挥神经功能保护作用。

Objective To investigate the effect of rat nerve growth factor(NGF)on the cerebral tissue inflammatory response,neuronal apoptosis and interleukin-6(IL-6),suppressor of cytokine signaling-3(SOCS-3)after intracerebral hemorrhage of caudate nucleus in rats.Methods 60 SD rats with caudate nucleus intracerebral hemorrhage established by non-heparinized autologous rat tail blood infusion were selected as the research objects,and they were randomly divided into sham operation group,model group and NGF group,with 20 rats in each group.The inflammatory response and neuronal apoptosis in the brain tissue around the hematoma were observed at 1 d,3 d and 5 d after the operation,and the expression of IL-6 and SOCS-3 in the brain tissue around the hematoma was detected by immunohistochemical staining.Results There was no significant difference in the water content of the brain tissue around the hematoma in the sham operation group at 3 time points after surgery(P>0.05);the water content of brain tissue around hematoma in model group and NGF group was significantly higher than that in sham operation group(P<0.05),and the water content of brain tissue around hematoma in NGF group was significantly lower than that in model group(P<0.05).The degree of brain tissue inflammation,edema and neuron cell necrosis in NGF group was significantly better than that in model group at each time point.The positive rate of TUNEL staining and positive number of IL-6 and SOCS-3 staining in the brain tissue around hematoma of model group and NGF group were significantly higher than those in sham group(P<0.05).The positive rate of TUNEL staining and the number of IL-6 staining positive cells were significantly lower in NGF group than those in model group(P<0.05),but the number of SOCS-3 staining positive cells was significantly higher than that in sham group(P<0.05).Conclusion NGF may play a protective role in neuroprotection by up-regulating the expression of SOCS-3 and down-regulating the expression of IL-6 to improve the inflammatory response of brain tissue after intracerebral hemorrhage and reduce neuronal apoptosis.