【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(xì)胞凋亡及凋亡相關(guān)蛋白Bcl-2、Bax的表達(dá)變化,以及對認(rèn)知功能水平的改善作用。方法:實(shí)驗(yàn)動(dòng)物隨機(jī)分入模型、1-MT、假手術(shù)三組中,每組10只。模型組及1-MT組行雙側(cè)頸總動(dòng)脈結(jié)扎術(shù)(Bilateral common carotid artery occlusion,BCCAO)制備2VO模型,假手術(shù)組在模型制備術(shù)中不結(jié)扎頸總動(dòng)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(rèn)知功能,TUNEL法觀察細(xì)胞凋亡,免疫組化法測定凋亡相關(guān)蛋白Bcl-2、Bax表達(dá)。結(jié)果:(1)水迷宮試驗(yàn):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(shù)組的(13.86±2.84)、(10.59±2.09)(P0.05);1-MT組穿越平臺(tái)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(shù)組的(4.90±0.66)(P0.05);1-MT組目標(biāo)象限停留時(shí)間(26.87±1.82),高于模型組的(21.56±1.74)(P0.05),低于假手術(shù)組的(28.01±1.44)(P0.05)。(2)Bax蛋白表達(dá)分別為假手術(shù)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(jì)學(xué)意義(P0.05);Bcl-2蛋白表達(dá)分別為假手術(shù)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(shù)組表達(dá)均明顯增加,差異有統(tǒng)計(jì)學(xué)意義(P0.05);凋亡細(xì)胞分別為假手術(shù)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(jì)學(xué)意義(P0.05)。結(jié)論:(1)2VO大鼠海馬CA1區(qū)出現(xiàn)細(xì)胞凋亡、凋亡蛋白表達(dá)增加,提示慢性腦低灌注大鼠病理性改變中存在細(xì)胞凋亡,可能與伴隨發(fā)生的認(rèn)知功能減低相關(guān);(2)使用1-MT可以減輕2VO大鼠認(rèn)知功能損害、減少海馬CA1區(qū)神經(jīng)細(xì)胞的凋亡及凋亡相關(guān)蛋白Bax、Bcl-2的表達(dá),但細(xì)胞凋亡的改善程度似乎不足以解釋認(rèn)知功能的改善程度,提示1-MT可能是通過細(xì)胞凋亡、炎性反應(yīng)等機(jī)制共同作用來影響認(rèn)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(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R749.1

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 張磊;章軍建;熊麗;劉暉;;慢性腦低灌注大鼠海馬縫隙連接蛋白32和36的表達(dá)變化[J];中國臨床神經(jīng)科學(xué);2009年06期

2 徐艷;章軍建;張磊;劉暉;楊英;熊麗;;綠茶多酚對慢性腦低灌注大鼠皮質(zhì)抗氧化能力的影響[J];臨床急診雜志;2010年05期

3 舒怡;張洪;章軍建;;慢性腦低灌注的實(shí)驗(yàn)研究進(jìn)展[J];中華腦血管病雜志(電子版);2010年03期

4 付劍亮,宋莉莉,邵福源;慢性腦低灌注對大鼠學(xué)習(xí)記憶及腦海馬組織中周期素依賴性激酶5表達(dá)的影響[J];中國臨床康復(fù);2005年20期

5 海艦,李世亭,潘慶剛,丁美修;慢性腦低灌注誘導(dǎo)血管生成的實(shí)驗(yàn)研究[J];中國神經(jīng)精神疾病雜志;2004年01期

6 徐立;劉建勛;叢偉紅;魏翠娥;;維腦康膠囊對慢性腦低灌注大鼠腦內(nèi)膽堿能系統(tǒng)及清除自由基能力的影響[J];中國中藥雜志;2008年05期

7 吳t，

本文編號(hào)：2357103