创伤性脑损伤后小鼠海马区Toll样受体4的表达与神经干细胞的变化

Expression of hippocampal toll - like receptors 4 and proliferation of neural progenitor cells in mouse model of traumatic brain injury

目的探讨小鼠创伤性脑损伤（TBI）后海马区Toll样受体4（TLR4）的表达及其与神经干细胞（NPCs）变化的关系。方法采用Mamarou自由落体打击法制备小鼠TBI模型，5-溴脱氧尿嘧啶核苷（BrdU）标记NPCs，免疫荧光染色、Western blot检测海马TLR4表达变化规律及NPCs时程变化特征。结果伤后1d海马区NPCs数量增多，3d达到高峰，7、14、21d逐渐减少（P〈0．05）。TLR4表达于海马区NPCs的胞膜和胞质，于伤后1d表达显著上调，高峰出现在伤后3d，于7、14、21d表达逐渐下调（P〈0．05）。结论TBI后海马区TLR4表达与NPCs变化趋势在时程上一致，TLR4可能是激活NPCs修复神经损伤的重要因素。

Objective To investigate the expression of hippocampal toll - like receptors 4 （TLR4） and the proliferation of neural progenitor cells （NPCs） in mouse model of traumatic brain injury （ TBI ）. Methods Adult male Balb/c mice were randomly divided into the sham groups and the 1st, 3rd, 7th, 14th, 21st days post - traumatic groups. The TBI mouse model was induced by Mamarou weight - drop device. NPCs were labeled with thymidine analog 5 - Bromo - 2 - deoxyUridine （BrdU）. The expression and distribution of BrdU and TLR4 in hippocampus were observed by inmmunofluorescence. The expression of TLR4 in protein level was detected by Western - blot. Results It was observed that TLR4 expressed on the NPCs in hippocampus by double - labeling inmmunofluorescence, and the expression of TLR4 protein in hippocampus raised at the 1st day, got to the peak around the 3rd day, then decreased over the 7th day, 14th day, and 21st day to a lower value but still higher than the sham group（ P 〈0. 05）. NPCs increased at the 1st post -traumatic day, reached the peak at the 3rd day, followed by a gradual reduction from the 3rd day to the 21st day when maintained a higher number than that of the sham group （ P 〈 0.05 ） . Conclusions TLR4 expressed on the NPCs in hippocampus, and the expression of hippocampal TLR4 varied in a similar temporal pattern with the proliferation of NPCs after injury. It suggested that hippocampal TLR4 might play a potential role in the endogenous neurogenesis after TBI.