本文選題：脂多糖　切入點：感染性腦損傷　出處：《華中科技大學(xué)》2008年博士論文

【摘要】： 第一部分脂多糖致幼年大鼠感染性腦損傷模型的建立 目的:探討一種新的模型制作方法—通過頸外動脈注射脂多糖建立幼年大鼠感染性腦損傷模型。方法:160只大鼠頸外動脈注射LPS及NS,至相應(yīng)時間點處死,制備腦組織標(biāo)本。檢測腦組織的伊文思藍(EB)含量,NSE、GFAP蛋白的表達量,確定大鼠感染性腦損傷模型的成功建立。結(jié)果:LPS組腦組織病理形態(tài)學(xué)改變明顯,腦組織EB含量,NES、GFAP蛋白表達量均較NS組高(P＜0.01)。結(jié)論:經(jīng)幼年大鼠頸外動脈注射LPS可以成功建立起穩(wěn)定、可靠的感染性腦損傷實驗動物模型。 第二部分脂多糖誘導(dǎo)的幼年大鼠神經(jīng)細胞凋亡及凋亡誘導(dǎo)因子的表達 目的:研究脂多糖誘導(dǎo)的幼年大鼠腦損傷過程中神經(jīng)細胞凋亡及凋亡誘導(dǎo)因子(AIF)的表達情況。方法:免疫組織化學(xué)技術(shù)檢測腦組織的AIF表達情況,TUNEL法檢測神經(jīng)細胞凋亡數(shù)。結(jié)果:與NS對照組相比,LPS組腦組織AIF蛋白表達及神經(jīng)細胞凋亡增多,差異有統(tǒng)計學(xué)意義(P＜0.01)。結(jié)論:凋亡參與了LPS致腦損傷的發(fā)生發(fā)展過程。AIF表達增加可能是導(dǎo)致神經(jīng)細胞凋亡的原因之一。 第三部分肝細胞生長因子對脂多糖致幼年大鼠感染性腦損傷的保護作用 目的:探討肝細胞生長因子(HGF)對脂多糖致幼年大鼠感染性腦損傷的保護作用。方法:經(jīng)大鼠頸外動脈注射LPS后即刻注射HGF,觀察腦組織EB含量、GFAP、NSE、AIF蛋白表達量,以及神經(jīng)細胞凋亡數(shù)。結(jié)果:HGF組各時間點腦組織EB含量、NSE、GFAP、AIF蛋白表達水平低于LPS組(P＜0.01)。結(jié)論:早期應(yīng)用肝細胞生長因子對LPS致幼年大鼠腦損傷具有保護作用。 第四部分褪黑素在LPS致幼年大鼠腦損傷中的保護作用 目的:探討褪黑素在LPS致腦損傷中的保護作用。方法:應(yīng)用LPS經(jīng)大鼠頸外動脈注射,分別提前及同時腹腔注射MT,觀察腦組織EB含量、GFAP、NSE、AIF蛋白表達量,以及神經(jīng)細胞凋亡數(shù)。結(jié)果:MT保護組24h、48h時間點腦組織EB含量、NSE、AIF、GFAP蛋白及凋亡表達變化均低于LPS組(P＜0.05),提前組和0小時組相比無統(tǒng)計學(xué)意義(P＞0.05)。結(jié)論:MT對LPS致幼年大鼠腦損傷具有保護作用,可能與其降低凋亡誘導(dǎo)因子AIF的表達,減少神經(jīng)細胞凋亡有關(guān),與抗生素同時應(yīng)用即可起到保護作用。
[Abstract]:The first part: establishment of infective brain injury model in juvenile rats induced by lipopolysaccharideAim: to explore a new method for the establishment of infective brain injury in young rats by injection of lipopolysaccharide into external carotid artery.Methods LPS and NSN were injected into the external carotid artery of 160 rats.The content of EBB in brain tissue and the expression of NSE-GFAP protein were measured to determine the successful establishment of rat model of infectious brain injury.Results the histopathologic changes of brain tissue in the group of 10% LPS were obvious, and the content of EB in brain tissue and the expression of GFAP protein in brain tissue were higher than those in group NS (P < 0.01).Conclusion: a stable and reliable animal model of infective brain injury can be successfully established by injecting LPS into the external carotid artery of young rats.The second part: apoptosis and expression of apoptosis-inducing factors in young rats induced by lipopolysaccharideAim: to study the expression of neuronal apoptosis and apoptosis-inducing factor (AIFs) during brain injury induced by lipopolysaccharide (LPS) in juvenile rats.Methods: immunohistochemical method was used to detect the expression of AIF in brain tissue and Tunel method was used to detect the number of neuronal apoptosis.Results: compared with the NS control group, the expression of AIF protein and the apoptosis of neurons in the LPS-treated group increased significantly (P < 0.01).Conclusion: apoptosis may be one of the causes of neuronal apoptosis.The third part: protective effect of hepatocyte growth factor on infectious brain injury induced by lipopolysaccharide in young ratsAim: to investigate the protective effect of hepatocyte growth factor (HGF) on infectious brain injury induced by lipopolysaccharide (LPS) in young rats.Methods: immediately after LPS was injected into the external carotid artery of rats, the expression of NSEAIF protein and the number of neuronal apoptosis were observed.Results the content of EB in brain tissue and the expression level of AIF protein in brain tissue of LPS group were lower than those of LPS group at different time points (P < 0.01).Conclusion: early application of hepatocyte growth factor has protective effect on brain injury induced by LPS in juvenile rats.The protective effect of melatonin on brain injury induced by LPS in juvenile ratsObjective: to investigate the protective effect of melatonin on brain injury induced by LPS.Methods: LPS was injected into the external carotid artery of rats and intraperitoneally injected in advance. The expression of EB protein and the number of apoptosis of neurons in brain tissue were observed.Results the changes of brain EB content and the expression of AIF-GFAP protein and apoptosis in brain tissue in the control group were lower than those in the LPS group (P < 0.05), but there was no significant difference between the early group and the 0-hour group (P > 0.05).ConclusionTwo one MT has protective effect on brain injury induced by LPS in juvenile rats, which may be related to the decrease of the expression of apoptosis inducing factor AIF and the decrease of neuronal apoptosis, which can be protected by the use of antibiotics at the same time.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2008
【分類號】：R-332;R741

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