摘要
目的探讨Toll样受体4表达变化对创伤性颅脑损伤后小鼠海马区髓样分化因子88(MYD88)的影响及其与神经干细胞的关系。方法采用随机数表法将C57BL/6小鼠分为3组,即为CLI-095组、溶剂组、假手术组,使用PCI-3000打击装置建立小鼠颅脑损伤模型,CLI-095组腹腔注射TLR4抑制剂CLI-095,溶剂组和假手术组腹腔注射溶剂,5-溴脱氧尿嘧啶核苷腹腔注射标记神经干细胞,采用免疫荧光染色、Western blot检测海马区MYD88表达变化情况以及神经干细胞变化的特征。结果Western Blotting检测及免疫荧光结果显示:假手术组MYD88表达未见明显变化,溶剂组MYD88表达升高(P〈0.05),CLI-095组MYD88蛋白水平较溶剂组下降(P〈0.05),但仍高于假手术组。免疫荧光结果显示:海马区CLI-095组5-溴脱氧尿嘧啶核苷阳性细胞表达数量较假手术组增多(P〈0.05),溶剂组5-溴脱氧尿嘧啶核苷阳性细胞表达数量相比CLI-095组减少,但仍高于假手术组(P〈0.05)。结论海马区MYD88的表达与神经干细胞变化相反,并证实抑制TLR4可能激活并引起神经干细胞的增殖,从而促进受损神经细胞的修复。
Objective To investigate the expression change of hippocampal toll-like receptor 4 (TLR4) and proliferation of neural stem cells (NSCs) in mouse model of traumatic brain injury (TBI). Methods Adult male C57BL/6 mice were randomly divided into "toll-like receptor 4 inhibitor CLI-095" group, solvent group andsham group according to random number table. The TBI mouse model was established using PCI-3000 device. Toll-like receptor 4 inhibitor CLI-095 was administered through intraperitoneal injection in the CLI-095 group and solvent was injected intraperitoneally in solvent and sham groups. NSCs were labeled with thymidine analog 5-Bromo-2-deoxyUridine (BrdU). The expression and distribution of BrdU and MYD88 in hippoeampus were assessed by inmmunofluoreseence. The expression of MYD88 protein was detected by Western blotting. Results MYD88 expression in the mouse hippocampus of the CLI-095 group was decreased following intraperitoneal injection of CLI-095, lower than the solvent group but higher than the sham ( P 〈 0.05 ) in Western Blotting. Numbers of neural cells in the hippoeampus increased after intraperitoneal injection of CLI-095 especially NSCs, which increased after intraperitoneal injection of CLI-095. Numbers of NSCs in the solvent groups was higher than the sham group but lower than the CLI-095 group (P 〈 0.05 ). Conclusion Expression of MYD88 in the hippocampus was negatively correlated with to NSC changes. It suggested that inhibition of TLR4 could activate expression of NSCs and increase their proliferation, and thus faeilitate repair of injured nerves.
出处
《中华神经外科杂志》
CSCD
北大核心
2016年第11期1156-1161,共6页
Chinese Journal of Neurosurgery
基金
国家自然科学基金(81171155)
关键词
颅脑损伤
TOLL样受体4
神经干细胞
小鼠
Traumatic brain injury
Toll-like receptors 4
Neural stein cells
Mice