创伤性脑损伤后大鼠海马区1-磷酸鞘氨醇受体1表达变化对神经干细胞增殖的影响  

Effects of sphingosine-l.phosphate receptor 1 alteration on proliferation of neural stem cells in hippocampus after traumatic brain injury

作　　者：叶玉勤[1,2] 苏鑫洪 段答[2] 杨永祥[1] 贺晓生[1] 

机构地区：[1]第四军医大学西京医院神经外科,西安710032 [2]解放军第一六三医院神经外科

出　　处：《中华创伤杂志》2017年第9期838-842,共5页Chinese Journal of Trauma

基　　金：国家自然科学基金（81171155,81471264）

摘　　要：目的探讨大鼠创伤性脑损伤（TBI）后海马区1-磷酸鞘氨醇受体1（S1PRl）的表达改变对神经干细胞（NSCs）增殖的影响。方法采用控制性皮层损伤法制备大鼠TBI模型。共纳入72只SD大鼠。按随机数字表法分为假损伤组、TBI组、TBI后S1PRl激动剂SEW2871干预组（TBI＋SEW组）和TBI后S1PR1抑制剂VPC23019干预组（TBI＋VPC组），每组18只。伤后7，14，21d，Western blot检测各组海马区SIPR1蛋白表达量，免疫荧光双标染色评估各组海马区NSCs的增殖情况。结果伤后7，14，21d，四组间s1PR1表达水平和NSCs增殖量差异均有统计学意义（P〈0．05）。其中伤后7d的差异变化最为显著：S1PR1的表达水平TBI组较假损伤组增加1．56倍，TBI＋SEW组进一步增加66．67％，TBI＋VPC组表达水平较TBI组则降低20．29％（P〈0．05）。NSCs的增殖数量TBI组较假损伤组增加2．08倍，TBI＋SEW组较TBI组增加36．75％，而TBI＋VPC组较TBI组减少18．77％（P〈0．05）。结论SIPR1是影响TBI后海马区NSCs增殖潜能的重要因素，激活S1PR1可能是促进TBI后神经再生与修复的有效途径。Objective To investigate the effects of sphingosine-1- phosphate receptor 1 （S1PR1） changes on the proliferation of endogenous neural stem cells （NSCs） in hippocampus after traumatic brain injury （TBI）. Methods Rat TBI models were constructed by the means of controlled cortical injury. A total of 72 rats were included and randomly divided into four groups： sham, TBI, TBI ＋ SEW （TBI ＋ S1PR1 agonist SEW2871 intervention） and TBI ＋ VPC group （TBI ＋ S1PRI antagonist VPC23019 intervention） , with 18 rats per group. The TBI model was induced by a control cortical injury device. The injured rats in TBI ＋ SEW group and TBI ＋ VPC group were respectively administrated with S1PRI agonist SEW2871 and antagonist VPC23019 at scheduled time points after TBI. Hippocampal S1PRI expression was detected by Western-blotting and the proliferation of NSCs was assessed by double-labeled immunoflnorescence staining at days 7,14 and 21 ＂after injury＇. Results At days 7, 14 and 21 after TBI,the hippocampal S1PR1 levels and NSCs proliferation amounts in sham, TBI, TBI ＋ SEW and TBI ＋ VPC groups were evidently different （P 〈 0.05 ）. In particular, the outstanding changes among the four groups above occurred at 7 d after injury were as following： S1PR1 expression in TBI group significantly increased by 1.56 times compared with that in sham group, and it was respectively up-regulated by 66.67% in TBI ＋ SEW group and down-regulated by 20.29% in TBI ＋ VPC group （ P 〈0.05 ）. The number of NSCs proliferation in TBI group was 2.08 times more than that in sham group, and it increased by 36.75% in TBI ＋ SEW group and reduced by 18.77% in TBI ＋ VPC group （P 〈 0.05 ）. Conclusion The expression of S1PR1 is closely associated with the proliferation of NSCs in hippocampus after TBI, indicating that S1PR1 activation may be an effective strategy to improve the post-traumatic neurogenesis.

关 键 词：脑损伤 神经干细胞 神经再生 1-磷酸鞘氨醇受体1 

分 类 号：R651.15[医药卫生—外科学]