中文摘要：

目的探讨肿瘤坏死因子受体1（tumornecrosisfactorreceptor1，TNFRl）在脑缺血小鼠血管发生和神经发生中的作用。方法24只野生型和24只TNFRl基因敲除小鼠随机分为假手术组和局灶性脑缺血组（每组12只），在脑缺血和假手术后第3天腹腔注射5-溴脱氧尿苷（5-bromode—oxyuridine，BrdU）。脑缺血后第7和第28天，应用葡萄糖载体-1（glucosetransporter-1，Glut-1）？BrdU免疫荧光染色双标记评价梗死周围区新生血管，标记BrdU检测侧脑室下区神经干细胞增殖，分别采用双皮质素（doublecortin，DCX）／BrdU和神经元核抗原（neuronalnucleiantigen，NeuN）／BrdU双标记检测神经干细胞迁移和存活。结果在正常情况下，野生型（418．000±28．404）和TNFR1基因敲除（528．0004-60．597）小鼠血管发生和室管膜下区（subventricularzone，SVZ）的BrdU阳性细胞数无显著性差异（t=-1．644，P=0．131）；脑缺血后第7天，TNFR1基因敲除小鼠Glut-1／BrdU阳性细胞数量显著少于野生型小鼠（14．833±2．182对27．5004±209；t=2．672，P=0．023），DCX／BrdU阳性细胞数也显著少于野生型小鼠（163．000±11．106对257．168±12．213；t=5．705，P=0．000）；脑缺血后第28天，TNFRl基因敲除小鼠NeuN／BrdU阳性细胞数显著少于野生型小鼠（6．0004-0．577对11．0004-1．571；t=2．988，P=0．014）。结论TNFR1可能在脑缺血后期的神经血管再生中起着促进作用。

英文摘要：

Objective To investigate the effect of tumor necrosis factor receptor 1 （TNFR1） in angiogenesis and neurogenesis during cerebral ischemia in mice. Methods Twenty-four wild-type and 24 TNFR1 knockout mice were randomly divided into either a sham operation group or a focal cerebral ischemia group （n = 12 in each group）. 5-bromodeoxyuridine （BrdU） was injected intraperitoneally at day 3 after cerebral ischemia and sham operation. At day 7 and 28 after cerebral ischemia, the double-label immunofluorescence staining of glucose transporter-1 （Glut-1）/BrdU was used to evaluate the angiogenesis surrounding the areas of infarction. A labeled BrdU was used to detect the neural stem cell proliferation in the subventricular zone. Double-labeled doublecortin （DCX）/BrdU and neuronal nuclei antigen （NeuN）/BrdU were used to detect the migration and survival of neural stem cells, respectively. Results Under the normal condition, there was no significant difference in angiogenesis and the number of BrdU-positive cells in the subependymal zone （SVZ） between the wild-type （418. 000 ±28. 404） and TNFRI knockout （528. 000 ±60. 597） mice （t = - 1. 644, P =0. 131）. At day 7 after cerebral ischemia, the number of Glut-1/BrdU-positive cells in the TNFR1 knockout mice was significantly less than that in the wild-type mice （14. 833 ±2. 182 vs. 27.5 ±4. 209） （t =2. 672, P=0. 023）, and the number of DCX/BrdU-positive cells was also significantly less than that in the wild-type mice （163. 000± 11. 106 vs. 257. 168 ±12. 213） （t = 5. 705, P = 0. 000）. At day 28 after cerebral ischemia, the number of NeuN/BrdU-positive cells in the TNFR1 knockout mice was significantly less than that in the wild- type mice （6. 000 ±0. 577 vs. 11. 000 ±1. 571） （t = 2. 988, P = 0. 014）. Conclusions TNFR1 may play a promoting role in the neurovascular regeneration in late cerebral ischemia.