作　　者： ; ; ; ; ; ;

机构地区： 中山大学附属第二医院

出　　处： 《中华神经医学杂志》 2008年第10期1013-1018,共6页

摘　　要： 目的探讨Kallikrein基因对脑缺血再灌注后梗死灶周围血管增生与局部脑血流灌注恢复的作用。方法建立大鼠脑缺血再灌注模型，术后将90只大鼠按照随机数字表法分为3组，每组30只，分别是空白对照组、注射生理盐水、注射pAdCMV-人组织激肽释放酶（HTK）组。各组大鼠又分为治疗后12h、24h及72h组，每组各10只。治疗前后行大鼠神经功能缺损评分。TTC染色方法测定脑梗死面积的变化，用免疫组化检测外源性HTK的表达以及局部血管内皮生长因子（VEGF）的表达，并通过^14C-iodoantipyrine微示踪技术检测局部脑血流灌注（rCBF）情况。结果与其他两组相比，pAdCMV—HTK组大鼠脑梗死面积在治疗后24h已有明显减小，72h后这种变化更明显，差异有统计学意义（P〈0．05）；在治疗后24h，pAdCMV—HTK组大鼠神经功能缺损评分明显低于生理盐水组及空白对照组，治疗后72h差异更明显，差异有统计学意义（P〈0．05）。VEGF阳性细胞主要分布于脑梗死灶周边皮质与部分白质；pAdCMV—HTK组VEGF表达在治疗后12h、24h、72h均明显高于生理盐水组及空白对照组，差异有统计学意义（P〈0．05）。各组缺血再灌注后脑梗死灶周围白质与皮质rCBF均较对侧稍减少：pAdCMV—HTK组治疗后12h，梗死灶周围白质与皮质rCBF较空白对照组与生理盐水组有增高，但不明显，差异无统计学意义（P〈0．05），而在治疗24h、72h后rCBF则明显增高，差异有统计学意义（P〈0．05）。结论在脑缺血再灌注后，Kallikrein基因转导可增加梗死灶周围脑组织的血管增生，改善rCBF，减小梗死面积，从而达到保护缺血神经细胞功能的作用。 Objective To investigate the effects of kallikrein gene transfer on microvascular proliferation around the cerebral infarct and on the recovery of regional cerebral blood flow （rCBF） following ischemia/reperfusion injury in rats. Methods The rats with cerebral ischemia/reperfusion injury induced by middle cerebral artery occlusion （MCAO） were randomly assigned into blank control group, saline group, and pAdCMV-HTK treatment group and received corresponding injections into the tissues around the infarct area. Each group was divided into 3 subgroups （n=10） for observation at 12, 24 and 72 h after the treatment. The neurological deficits of the rats before and aider the treatment were evaluated using neurological severity scores （NSS）, and the expressions of exogenous human tissue kallikrein （HTK） and vascular endothelial growth factor （VEGF） in the brain tissues were detected immunohistochemically. TTC staining was performed to measure the changes in the infarct size. ^14C-iodoantipyrine tracing technique was used to define the rCBF in the rats. Results Compared to the blank control group, the cerebral infarct size was significantly reduced in pAdCMV-HTK group 24 h after the treatment, and was further reduced at 72 h （P〈0.05）. At 24 h after the treatment, the NSS in pAdCMV-HTK group was significantly lower than that in the blank control and saline groups （P〈0.05）, and was further reduced at 72 h （P〈0.01）. After MCAO, the VEGF-positive cells were found mostly in the cortex and the white matter around the infarct area. The expression of VEGF in pAdCMV-HTK group was markedly higher than that in the other two groups at 12, 24, and 72 h after the treatment （P〈0.05）. In all the 3 groups, the rCBF around the infarct was slightly decreased as compared to that in the contralateral hemisphere, pAdCMV-HTK slightly increased the rCBF 12 h after the injection （P〉0.05）, and significant increase in the rCBF occurred 24 h and 72 h after the injection （P〈0.05）. Conclusion

关 键 词： 脑缺血再灌注 腺病毒介导 激肽释放酶 血管内皮生长因子

领　　域： [生物学]