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  本文選題：膽堿能抗炎通路 + 腦缺血再灌注　； 參考：《北京市結(jié)核病胸部腫瘤研究所》2008年碩士論文

【摘要】： 目的:應(yīng)用側(cè)腦室注射M1型膽堿能受體激動劑McN-A-343、M2型膽堿能受體拮抗劑美索曲明(Methoctramine)以及α7亞單位的N型膽堿能受體激動劑膽堿(Choline)的方法激活膽堿能抗炎通路(cholinergic anti-inflammatory pathway,CAP),通過檢測大鼠左側(cè)海馬、心、肝、肺、腎和血漿中腫瘤壞死因子-α(tumor necrosis factor alpha, TNF-α)、白介素-1β(interleukin-1β,IL-1β)含量及右側(cè)海馬CA1區(qū)細(xì)胞凋亡數(shù),進(jìn)一步探討CAP對大鼠腦缺血再灌注損傷的影響。 方法:健康成年雄性Sprague-Daewley大鼠25只,隨機(jī)分為5組(n=5):假手術(shù)組(SHAM組)、腦缺血再灌注組(I/R組)、美索曲明組(MET組)、McN-A-343組(MA343組)和膽堿組(CHO組)。4-VO[1]法建立全腦缺血再灌注損傷模型,電凝大鼠雙側(cè)椎動脈(SHAM組除外),于缺血前15min分別經(jīng)側(cè)腦室向MET組、MA343組及CHO組注射Methoctramine(500ng/kg,10μl)、McN-A-343(500ng/kg,10μl)及Choline(500ng/kg,10μl),SHAM組及I/R組注射生理鹽水10μl。除SHAM組外,各組夾閉雙側(cè)頸總動脈20min后再灌注。再灌注6h后,斷頭處死動物,采集標(biāo)本。放射免疫法(RIA)檢測左側(cè)海馬、心、肝、肺、腎和血漿中TNF-α、IL-1β含量。TdT介導(dǎo)的dUTP缺口末端標(biāo)記技術(shù)(Terminal deoxynucleotidyl transferase fluorescein-12-dUTP nick end labeling, TUNEL)染色檢測右側(cè)海馬CA1區(qū)細(xì)胞凋亡數(shù)。 結(jié)果:再灌注后,MET組和MA343組海馬、心、肝、腎組織勻漿及血漿TNF-α、IL-1β含量顯著低于I/R組(P0.05),肺組織TNF-α、IL-1β含量差異無統(tǒng)計(jì)學(xué)意義(P0.05)。CHO組海馬TNF-α、IL-1β含量較I/R組有所降低(P0.05),而心、肺、肝、腎及血漿TNF-α、IL-1β含量差異無統(tǒng)計(jì)學(xué)意義。與I/R組相比,MET、MA343及CHO組海馬CA1區(qū)凋亡細(xì)胞數(shù)目減少(P0.05)。 結(jié)論:TNF-α、IL-1β的釋放是腦缺血再灌注損傷的重要機(jī)制之一,CAP對腦缺血再灌注引發(fā)的局部及全身炎癥反應(yīng)均具有保護(hù)作用,對細(xì)胞凋亡有間接抑制作用。其機(jī)制與Methoctramine、McN-A-343和Choline激活CAP后抑制缺血再灌注TNF-α、IL-1β的釋放有關(guān)。
[Abstract]:Objective: to activate the cholinergic anti-inflammatory pathwayCAPPAP pathway by intracerebroventricular injection of the M1 type cholinergic receptor agonist McN-A-343M 2 cholinergic receptor antagonist methoctramine and the N-type cholinergic receptor agonist choline of 偽 7 subunit.By detecting the left hippocampus of rats,The contents of TNF- 偽 tumor necrosis factor alpha, TNF- 偽, interleukin-1 尾 interleukin-1 尾 interleukin-1 尾 IL-1 尾 in heart, liver, lung, kidney and plasma and the number of apoptosis in the right hippocampal CA1 region were studied to investigate the effect of CAP on cerebral ischemia-reperfusion injury in rats.Methods: Twenty-five healthy adult male Sprague-Daewley rats were randomly divided into 5 groups: sham-operated group (sham group), cerebral ischemia-reperfusion group (I / R) group, misotromine group (MET group) and choline group (Cho group) and choline group (Cho group. 4-VO [1] method) to establish global cerebral ischemia-reperfusion injury model.Before ischemia, 15min was injected into MET group (MA343 group) and CHO group (10 渭 g / kg), Choline500ngSHAM group (10 渭 l) and Choline 500ng / kg SHAM group (10 渭 l) and I / R group (10 渭 l).With the exception of SHAM group, 20min of bilateral common carotid artery was clipped and reperfusion in each group.After reperfusion for 6 hours, the animals were killed and the specimens were collected.The terminal deoxynucleotidyl transferase fluorescein-12-dUTP nick end labeling (Tunel) in left hippocampus, heart, liver, lung, kidney and plasma mediated by terminal deoxynucleotidyl transferase fluorescein-12-dUTP nick end labeling (Tunel) were used to detect the apoptosis of CA1 in the right hippocampus.Results: after reperfusion, the contents of TNF- 偽 IL-1 尾 in hippocampus, heart, liver, kidney homogenate and plasma in the met group and the MA343 group were significantly lower than those in the I / R group (P 0.05). There was no significant difference in the content of TNF- 偽 and IL-1 尾 between the two groups (P 0.05), but the contents of TNF- 偽 IL-1 尾 in the heart, lung, liver, liver, and lung were significantly lower than those in the I / R group.There was no significant difference in the contents of TNF- 偽 and IL-1 尾 between kidney and plasma.Compared with the I / R group, the number of apoptotic cells in the hippocampal CA1 region of CHO group was significantly lower than that of METMA343 group.Conclusion the release of IL-1 尾 from TNF- 偽 is one of the important mechanisms of cerebral ischemia-reperfusion injury. CAP has protective effect on local and systemic inflammation induced by cerebral ischemia-reperfusion, and indirectly inhibits apoptosis.The mechanism is related to the inhibition of TNF- 偽 IL-1 尾 release after activation of CAP by method minefield McN-A-343 and Choline.
【學(xué)位授予單位】：北京市結(jié)核病胸部腫瘤研究所
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2008
【分類號】：R741

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