摘要
目的探讨阻断星形胶质细胞内谷氨酸-谷氨酰胺循环在脑缺血-再灌注损伤中的神经保护作用。方法采用大脑中动脉栓塞（MCAO）线栓法制备脑缺血-再灌注损伤动物模型,首次Longa神经功能评分1-3分者为模型建立成功。采用随机数字表法,将清洁级健康雄性SD大鼠30只完全随机分为空白对照组、假手术组、MCAO模型组、再灌注0 h和1 h给药组,每组各6只。MCAO模型组为栓线穿过大脑中动脉起始段并达大脑前动脉近端;假手术组为栓线至颈总动脉内,不阻断大脑中动脉血流;再灌注0 h给药组为拔出栓线后立即腹腔注射L-蛋氨酸砜亚胺（MSO）50 mg/kg;再灌注1 h给药组为拔出栓线再灌注1 h后,腹腔注射MSO 50 mg/kg。拔出栓线24 h后,行神经功能评分检测、脑梗死体积测定、谷氨酰胺合成酶（GS）活性和凋亡细胞检测。结果空白对照组和假手术组神经功能评分正常,脑组织内均未见梗死灶及凋亡细胞,GS酶活性差异无统计学意义（P〉0.05）;MCAO模型组GS活性低于空白对照组和假手术组,差异均有统计学意义[（176.7±2.8）×10^3U/g比（1 9 8.8±1.2）×10^3U/g和（1 9 6.1±2.6）×10^3U/g,均P〈0.0 1]。再灌注0 h和1 h给药组神经功能评分、脑梗死体积比、GS活性、凋亡细胞百分比分别与MCAO模型组比较,差异均有统计学意义[（1.2±0.4）分和（1.3±0.8）分比（2.5±0.6）分,（10.0±2.0）%和（20.9±1.1）%比（26.8±1.5）%,（22.2±1.2）×10^3U/g和（22.0±1.2）×10-3U/g比（176.7±2.8）×10^3U/g,（2.35±0.23）%和（4.36±0.30）%比（7.85±0.27）%,均P〈0.05];再灌注1 h给药组神经功能评分、脑梗死体积比、GS活性与再灌注0 h给药组比较,差异均无统计学意义（均P〉0.05）;再灌注0 h和1 h给药组凋亡细胞百分比差异有统计学意义（P〈0.01）。结论抑制GS酶活性,可阻断星形胶质细胞内谷氨酸-谷氨酰胺循环,发挥神经保护作用。
Objective To investigate the neuroprotective effect of blocking Glutamate-Glutamine shuttle in astrocytes against cerebral ischemia-reperfusion injury. Methods Cerebral ischemia-reperfusion injury model was generated via the surgery of middle cerebral artery occlusion （MCAO） for 1 h and then reperfusion of blood for 24 h. The model with 1 to 3 score after the first Longa neural function test was established successfully. A total of 30 SD rats of cleaning grade were completely randomly divided into 5 groups by random number table method,6 rats in each group：naive group, sham group, MCAO model group ,reperfusion 0 h MSO intraperitoneal injection （i. p. ） group and reperfusion 1 h MSO i. p. group. The silk thread in MCAO model group passed through the start segment of the middle cerebral artery and reached the proximal segment of the anterior cerebral artery. The silk thread was inserted in the common carotid artery without blocking the blood flow of the middle cerebral artery in sham group. After pulling out the silk thread in reperfusion 0 h MSO i. p. group, Lmethionine （MSO） 50 mg/kg was intraperitoneally injected immediately. L-methionine （MSO） 50 mg/kg was intraperitoneally injected after reperfusion of blood for 1 h in reperfusion lh MSO i. p. group. Neural function score, cerebral infarct volume, glutamine synthetase （GS） special activity and the percentage of apoptotic cells were detected after reperfusion for 24 h. Results Neural function score was normal in both naive group and sham group, and no cerebral infarction and apoptosis cells were observed, there was no statistic difference in the GS special activity between these two groups（P 〉 0.05） ;the GS special activity was decreased in the MCAO model group compared with that in the naive group （ 1176. 7 ± 2. 8 ] ×10^3 U/g vs. [ 198. 8 ± 1.2 ] × 10^3 U/g, P 〈 0. 01 ） and sham group （ [ 176. 7 ± 2. 8 ] × 10^3 U/g vs. [ 196. 1 ± 2. 6 ] ×10^3 U/g,P 〈 0. 01 ）. Reperfusion 0 h and 1 h MSO i. p. group had significan
出处
《中国脑血管病杂志》
CAS
CSCD
北大核心
2016年第4期198-203,共6页
Chinese Journal of Cerebrovascular Diseases
基金
国家自然科学基金(81371230)
