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阻断谷氨酸-谷氨酰胺循环对大鼠脑缺血-再灌注损伤的神经保护作用

发布时间:2018-10-17 11:20
【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(P0.05);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)×1 0~3U/g比(1 9 8.8±1.2)×1 0~3U/g和(1 9 6.1±2.6)×1 03U/g,均P0.0 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P0.05];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P0.05);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(P0.01)。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。
[Abstract]:Objective to investigate the neuroprotective effect of blocking glutamate-glutamine circulation in astrocytes during cerebral ischemia-reperfusion injury. Methods the animal model of cerebral ischemia-reperfusion injury was established by middle cerebral artery embolization (MCAE) with (MCAO) thread embolization. The model was successfully established with the first Longa score of 1 ~ 3. Thirty healthy male SD rats of clean grade were randomly divided into control group, sham operation group, MCAO model group, 0 h and 1 h reperfusion group. There were 6 rats in each group. The MCAO model group was made up to the proximal end of the anterior cerebral artery through the starting segment of the middle cerebral artery, and the sham-operation group did not block the blood flow of the middle cerebral artery from the thrombus to the common carotid artery. After 0 h reperfusion, L-methionine sulfone imide (MSO) 50 mg/kg; was injected intraperitoneally immediately after pulling out the thread, and then 1 h after reperfusion, MSO 50 mg/kg. was injected intraperitoneally. The nerve function score, cerebral infarction volume, glutamine synthase (GS) activity and apoptotic cells were measured 24 hours later. Results the neurological function scores in the blank control group and the sham operation group were normal, and no infarct or apoptotic cells were found in the brain tissue. There was no significant difference in the activity of GS enzyme between the two groups (P0.05) the GS activity in the); MCAO model group was lower than that in the blank control group and the sham-operation group. The differences were statistically significant [(176.7 卤2. 8) 脳 1 0~3U/g vs (19. 8. 8 卤1. 2) 脳 1 0~3U/g and (19. 6.1 卤2. 6) 脳 10 ~ 3 U / g, both P 0. 01]. The neurological function score, cerebral infarction volume ratio, GS activity and percentage of apoptotic cells in the 0 h and 1 h reperfusion groups were compared with those in the MCAO model group. 宸紓鍧囨湁缁熻瀛︽剰涔塠(1.2卤0.4)鍒嗗拰(1.3卤0.8)鍒嗘瘮(2.5卤0.6)鍒,

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