CAJ | 학술논문

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7 d 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14 d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.
목적 관찰외원성격태석방매대대서피질경사후내원성신경재생적영향.방법 용역졸중형신혈관성고혈압대서,수궤분위국조성대뇌피질경사+격태석방매치료조、대뇌피질경사+용제대조조화가수술대조조,소유대서균복강주사5-추탈양뇨밀정핵감(BrdU)용이표기신증식세포.분별재불동시간점행신경공능평분후처사대서,측뇌경사조체적,병관찰경사측측뇌실하구(SVZ)BrdU+、BrdU+/DCX+표체이급경사조주BrdU+、BrdU+/NeuN+표체.결과 여용제대조조급가수술대조조상비,격태석방매치료촉진료술후불동시간점경사측SVZ BrdU+、BrdU+/DCX+화경사조주BrdU+、BrdU+/NeuN+표체(술후7 d SVZ BrdU+분별위304.0±73.9、167.0±32.2화56.0±12.2,분별q=7.165、12.916、5.751,균P<0.05;SVZ BrdU+/DCX+분별위225.0±13.6、98.0±9.6화23.0±5.6,분별q=30.731、48.735화18.004,균P<0.01;경사조주BrdU+위490.0±82.0、308.0±51.5화49.0±9.5,분별q=7.920、19.184、11.264,균P<0.01;술후14 d경사조주BrdU+/NeuN+위21.0±3.4화13.0±2.6,t=4.568,P=0.001),병촉진료신경공능회복.결론 외원성격태석방매가촉진대서피질경사후내원성신경간세포활화,병개선신경공능.
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.