中文摘要：

目的在大鼠局灶性脑缺血模型中观察低氧反应元件（HRE）介导的神经营养因子-3（NT-3）缺血/低氧调控表达及其对缺血再灌注脑损伤的保护作用。方法将重组反转录病毒（RV-5HRE-NT3及RV-5HRE-EGFP）或0.9%氯化钠溶液（对照组）注射入大鼠脑内3 d后,用大脑中动脉线栓阻塞法（t MCAO）制作大鼠局灶性脑缺血再灌注损伤模型。用免疫组织化学染色法和Western blot法检测NT-3的表达,用TTC染色法检测脑梗死体积,用TUNEL染色法检测细胞凋亡,用Reglodi评分法检测大鼠神经功能情况。结果大鼠t MCAO 3 d后RV-5HRE-NT3组中NT-3阳性细胞数明显高于对照组和RV-5HRE-EGFP组,且着色较深;t MCAO后第1、3、7和14天,RV-5HRE-NT3组中的NT-3蛋白表达均明显高于对照组和RV-5HRE-EGFP组（P〈0.05）。在RV-5HRE-NT3组中,t MCAO 3 d大鼠脑梗死体积百分比明显减小（P〈0.05）,t MCAO 3和7 d后缺血半暗带凋亡细胞百分比也明显减少（P〈0.05）。RV-5HRE-NT3注射可以改善大鼠t MCAO后的神经功能障碍。结论 HRE介导的NT-3低氧反应性表达上调可以减轻大鼠局灶性脑缺血再灌注脑损伤。

英文摘要：

Objective To investigate the neuroprotective effects of neurotrophin-3 （NT-3） expression controlled by five copies of the hypoxia-responsive elements after focal cerebral ischemia. Methods Three groups of rats re- ceived RV-5H-NT3, RV-5H-EGFP or saline injection. Three days after gene transfer, the rats underwent 90 min of transient middle cerebral artery occlusion （tMCAO） , followed by 1 -28 days of reperfusion. Immunohistostaining and western blotting were performed to detect ischemia/hypoxia-regulated expression of NT-3 controlled by HRE The volume of brain infarction and the apoptosis were analysised by TYC and TUNEL staining. The neurological scoring was determined by neurological behavior tests. Results Three days after tMCAO, brain NT-3 expression was significantly increased in the RV-5HNT3-transduced animals compared with the RV-5H-EGFP or saline group （P 〈0.05 ）, and brain infaret wolume was smaller in the RV-5H-NT3-transdueed group than the RV-5H-EGFP or saline group （P 〈0.05 ）. The percentage of TUNEL-positive cells was reduced in RV-5tf-NT3-transduced brains compared with lhe RV-5 HEGFP or saline group 3 and 7 days after IMCAO （ P 〈 0.05 ）. Furthermore, the neurolog- ical status of [lV-5H-NT3-transduced rats was better than that of I1V-5｜｜-EGFP- or saline-transduced animals from 1 day to 4 weeks after tMCAO （P 〈 0.05 ）. Conclusions ttRE may modulate NT-3 expression in the isehemic brain tissue and that the up-regulated NT-3 may effectively improve neurological status following IMCAO due to de- creased initial damage.