【摘要】：目的探討阻斷星形膠質(zhì)細胞內(nèi)谷氨酸-谷氨酰胺循環(huán)在腦缺血-再灌注損傷中的神經(jīng)保護作用。方法采用大腦中動脈栓塞(MCAO)線栓法制備腦缺血-再灌注損傷動物模型,首次Longa神經(jīng)功能評分1~3分者為模型建立成功。采用隨機數(shù)字表法,將清潔級健康雄性SD大鼠30只完全隨機分為空白對照組、假手術(shù)組、MCAO模型組、再灌注0 h和1 h給藥組,每組各6只。MCAO模型組為栓線穿過大腦中動脈起始段并達大腦前動脈近端;假手術(shù)組為栓線至頸總動脈內(nèi),不阻斷大腦中動脈血流;再灌注0 h給藥組為拔出栓線后立即腹腔注射L-蛋氨酸砜亞胺(MSO)50 mg/kg;再灌注1 h給藥組為拔出栓線再灌注1 h后,腹腔注射MSO 50 mg/kg。拔出栓線24 h后,行神經(jīng)功能評分檢測、腦梗死體積測定、谷氨酰胺合成酶(GS)活性和凋亡細胞檢測。結(jié)果空白對照組和假手術(shù)組神經(jīng)功能評分正常,腦組織內(nèi)均未見梗死灶及凋亡細胞,GS酶活性差異無統(tǒng)計學意義(P0.05);MCAO模型組GS活性低于空白對照組和假手術(shù)組,差異均有統(tǒng)計學意義[(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給藥組神經(jīng)功能評分、腦梗死體積比、GS活性、凋亡細胞百分比分別與MCAO模型組比較,差異均有統(tǒng)計學意義[(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給藥組神經(jīng)功能評分、腦梗死體積比、GS活性與再灌注0 h給藥組比較,差異均無統(tǒng)計學意義(均P0.05);再灌注0 h和1 h給藥組凋亡細胞百分比差異有統(tǒng)計學意義(P0.01)。結(jié)論抑制GS酶活性,可阻斷星形膠質(zhì)細胞內(nèi)谷氨酸-谷氨酰胺循環(huán),發(fā)揮神經(jīng)保護作用。
[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 鹵2. 8) 脳 1 0~3U/g vs (19. 8. 8 鹵1. 2) 脳 1 0~3U/g and (19. 6.1 鹵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紓鍧囨湁緇熻瀛︽剰涔塠(1.2鹵0.4)鍒嗗拰(1.3鹵0.8)鍒嗘瘮(2.5鹵0.6)鍒，

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