摘要
目的观察外源性激肽释放酶对大鼠皮质梗死后内源性神经再生的影响。方法用易卒中型肾血管性高血压大鼠，随机分为局灶性大脑皮质梗死＋激肽释放酶治疗组、大脑皮质梗死＋溶剂对照组和假手术对照组，所有大鼠均腹腔注射5-溴脱氧尿嘧啶核苷（BrdU）用以标记新增殖细胞。分别在不同时间点行神经功能评分后处死大鼠，测脑梗死灶体积，并观察梗死侧侧脑室下区（SVZ）BrdU^＋、BrdU^＋／DCX^＋表达以及梗死灶周BrdU^＋、BrdU^＋／NeuN^＋表达。结果与溶剂对照组及假手术对照组相比，激肽释放酶治疗促进了术后不同时间点梗死侧SVZ BrdU^＋、BrdU^＋／DCX^＋和梗死灶周BrdU^＋、BrdU^＋／NeuN^＋表达（术后7d SVZ BrdU^＋分别为304．0±73．9、167．0±32．2和56．0±12．2，分别q=7．165、12．916、5．751，均P〈0．05；SVZ BrdU^＋／DCX^＋分别为225．0±13．6、98．0±9．6和23．0±5．6，分别q=30．731、48．735和18．004，均P〈0．01；梗死灶周BrdU^＋为490．0±82．0、308．0±51．5和49．0±9．5，分别q=7．920、19．184、11．264，均P〈0．01；术后14d梗死灶周BrdU^＋／NeuN^＋为21．0±3．4和13．0±2．6，t=4．568，P=0．001），并促进了神经功能恢复。结论外源性激肽释放酶可促进大鼠皮质梗死后内源性神经干细胞活化，并改善神经功能。
Objective To investigate whether delayed treatment with exogenous kallikrein on neurogenesis after focal cortical infarction in stroke-prone renovascular hypertensive rats （RHRSP） . Methods Seventy-two RHRSP were divided into 3 groups. Twenty-four rats were given human tissue kallikrein （ 1.6×10^-2 PNAU/kg） and 24 rats were given vehicle through tail venous daily for 2 or 6 days consecutively starting at the 24th hour after distal middle cerebral artery occlusion （MCAO）. 24 rats underwent sham-operation. Cell proliferation was examined by using 5＇-bromo-2＇-deoxyuridine （BrdU, 50 mg/kg）. Rats were respectively sacrificed 3, 7, 14 or 28 days after MCAO. Results Treatment with kallikrein significantly increased the number of BrdU^＋ cells in the ipsilateral subventricular zone （SVZ） （304. 0±73.9 vs 167.0±32. 2 vs 56. 0±12. 2 at 7 d after operation, q =7. 165, 12. 916 and 5. 751 respectively,all P 〈0. 05） and in the peri-infarction region （490. 0±82.0 vs 308.0±51.5 vs 49.0±9. 5 at 7 d after operation, q =7. 920, 19. 184 and 11. 264 respectively, all P 〈0.01 ）, and increased the number of BrdU^＋/DCX^＋ cells （225.0±13. 6 vs 98.0±9. 6 vs 23.0±5.6 at 7 d after operation, q = 30. 731,48.735 and 18. 004 respectively, all P 〈 0. 01 ） in the ipsilateral SVZ compared with the vehicle group or the sham-operated group, which began on the 3 day, peaked in 7--14 days after MCAO, and then gradually decreased. Compared with the vehicle group, exogenous kallikrein markedly increased the number of BrdU^＋/NeuN^＋ cells （21.0±3.4 vs 13. 0±2. 6 at 14 d, P =0. 001 ） in the peri-infarction region after MCAO. The kallikrein group showed a better functional improvement than the vehicle group after stroke （all P 〈 0.05）. Conclusion Our study suggests that administration of exogenous kallikrein at 24 h after cortical infarction enhances the SVZ neuroblasts proliferation, migration, and selective differentiation and improves functional recovery after stroke.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2008年第9期628-632,共5页
Chinese Journal of Neurology
基金
国家自然科学基金资助项目（39940012,30271485,30770764）
美国CMB基金资助项目（00-730）
卫生部临床学科重点基金资助项目（2004）
广东省自然科学基金资助项目（990065,21906,2003C30610）
广州市科技攻关项目（2006Z-E0111和Z1-E0113）
关键词
脑梗塞
激肽释放酶类
神经再生
细胞增殖
细胞分化
大鼠
Cerebral infarction
Kallikreins
Nerve regeneration
Cell proliferation
Cell differentiation
Rats
