【摘要】：目的:觀察慢性腦低灌注模型2VO(2-vessel occlusion)大鼠使用犬尿氨酸通路(Kynurenine pathway,KP)限速酶吲哚胺-2,3-雙加氧酶(indoleamine2,3-dioxygenase,IDO)抑制劑1-甲基色氨酸(1-MT)后海馬CA1區(qū)細胞凋亡及凋亡相關蛋白Bcl-2、Bax的表達變化,以及對認知功能水平的改善作用。方法:實驗動物隨機分入模型、1-MT、假手術三組中,每組10只。模型組及1-MT組行雙側頸總動脈結扎術(Bilateral common carotid artery occlusion,BCCAO)制備2VO模型,假手術組在模型制備術中不結扎頸總動脈。1-MT組予1-MT混懸液灌胃,其余兩組予生理鹽水灌胃,共14天。Morris水迷宮檢測認知功能,TUNEL法觀察細胞凋亡,免疫組化法測定凋亡相關蛋白Bcl-2、Bax表達。結果:(1)水迷宮試驗:1-MT組第4、5天的逃避潛伏期分別為(17.93±3.24)、(13、11±1.85),低于模型組的(42.31±6.03)、(41.12±4.56)(P0.05),高于假手術組的(13.86±2.84)、(10.59±2.09)(P0.05);1-MT組穿越平臺位置次數(shù)(4.70±0.60),高于模型組的(2.50±0.45)(P0.05),低于假手術組的(4.90±0.66)(P0.05);1-MT組目標象限停留時間(26.87±1.82),高于模型組的(21.56±1.74)(P0.05),低于假手術組的(28.01±1.44)(P0.05)。(2)Bax蛋白表達分別為假手術組(6.25±1.04)、模型組(56.43±2.62)、1-MT組(30.16±2.17),各組間比較差異均有統(tǒng)計學意義(P0.05);Bcl-2蛋白表達分別為假手術組(9.97±2.66)、模型組(48.67±5.99)、1-MT組(32.67±4.71),模型組及1-MT組比假手術組表達均明顯增加,差異有統(tǒng)計學意義(P0.05);凋亡細胞分別為假手術組(1.79±0.41)、模型組(14.13±1.44)、1-MT組(7.80±1.38),各組間比較差異均有統(tǒng)計學意義(P0.05)。結論:(1)2VO大鼠海馬CA1區(qū)出現(xiàn)細胞凋亡、凋亡蛋白表達增加,提示慢性腦低灌注大鼠病理性改變中存在細胞凋亡,可能與伴隨發(fā)生的認知功能減低相關;(2)使用1-MT可以減輕2VO大鼠認知功能損害、減少海馬CA1區(qū)神經細胞的凋亡及凋亡相關蛋白Bax、Bcl-2的表達,但細胞凋亡的改善程度似乎不足以解釋認知功能的改善程度,提示1-MT可能是通過細胞凋亡、炎性反應等機制共同作用來影響認知功能。
[Abstract]:Objective: to observe the rate-limiting enzyme indoleamine-3-dioxygenase (indoleamine2,3-dioxygenase,) of canine uremic acid pathway (Kynurenine pathway,KP) in chronic cerebral hypoperfusion model 2VO (2-vessel occlusion) rats. IDO) inhibitor 1-methyltryptophan (1-MT) induced apoptosis and the expression of apoptosis-related protein (Bcl-2,Bax) in hippocampal CA1 and the improvement of cognitive function. Methods: experimental animals were randomly divided into three groups, 1-MTand sham-operation groups, 10 rats in each group. Model group and 1-MT group were treated with bilateral common carotid artery ligation (Bilateral common carotid artery occlusion,BCCAO) to make 2VO model, sham operation group did not ligate common carotid artery during model preparation, and 1-MT group was given 1-MT suspension intragastric perfusion. The other two groups were perfused with normal saline for 14 days. The cognitive function was detected by Morris water maze, apoptosis was observed by TUNEL method, and the expression of apoptosis-related protein Bcl-2,Bax was detected by immunohistochemistry. Results: (1) Water labyrinth test: the escape latency of the 1-MT group was (17.93 鹵3.24), () 1311 鹵1.85 on the 4th day, which was lower than that of the model group (42.31 鹵6.03), (41.12 鹵4.56) (P0.05). It was higher than the sham-operated group (13.86 鹵2.84), (, 10.59 鹵2.09, P0.05). The frequency of crossing the platform position in 1-MT group (4.70 鹵0.60) was higher than that in model group (2.50 鹵0.45) (P0.05), and lower than that in sham-operated group (4.90 鹵0.66) (P0.05). The target quadrant residence time of 1-MT group (26.87 鹵1.82) was higher than that of model group (21.56 鹵1.74) (P0.05). The expression of Bax protein in sham-operated group (28.01 鹵1.44) (P0.05). (2) was (6.25 鹵1.04), model group (56.43 鹵2.62), 1-MT group (30.16 鹵2.17). The differences among groups were statistically significant (P0.05). The expression of Bcl-2 protein in sham-operation group (9.97 鹵2.66), model group (48.67 鹵5.99) and 1-MT group (32.67 鹵4.71) was significantly higher than that in model group and 1-MT group. The difference was statistically significant (P0.05). The apoptotic cells in sham-operated group (1.79 鹵0.41), model group (14.13 鹵1.44) and 1-MT group (7.80 鹵1.38) were significantly different (P0.05). Conclusion: (1) apoptosis and increased expression of apoptotic protein in the CA1 area of hippocampus of 2VO rats suggest that there is apoptosis in the pathological changes of chronic cerebral hypoperfusion rats, which may be related to the associated decreased cognitive function. (2) 1-MT could attenuate the cognitive impairment of 2VO rats, and reduce the apoptosis of neurons and the expression of apoptosis-related protein Bax,Bcl-2 in hippocampal CA1 area. However, the degree of improvement of apoptosis seems to be insufficient to explain the improvement of cognitive function, suggesting that 1-MT may affect cognitive function through the mechanisms of apoptosis and inflammatory response.
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R749.1

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