脂多糖致幼年大鼠脑损伤中的细胞凋亡及干预性研究

发布时间：2018-04-02 15:21

本文选题：脂多糖　切入点：感染性脑损伤　出处：《华中科技大学》2008年博士论文

【摘要】： 第一部分脂多糖致幼年大鼠感染性脑损伤模型的建立目的:探讨一种新的模型制作方法—通过颈外动脉注射脂多糖建立幼年大鼠感染性脑损伤模型。方法:160只大鼠颈外动脉注射LPS及NS,至相应时间点处死,制备脑组织标本。检测脑组织的伊文思蓝(EB)含量,NSE、GFAP蛋白的表达量,确定大鼠感染性脑损伤模型的成功建立。结果:LPS组脑组织病理形态学改变明显,脑组织EB含量,NES、GFAP蛋白表达量均较NS组高(P＜0.01)。结论:经幼年大鼠颈外动脉注射LPS可以成功建立起稳定、可靠的感染性脑损伤实验动物模型。第二部分脂多糖诱导的幼年大鼠神经细胞凋亡及凋亡诱导因子的表达目的:研究脂多糖诱导的幼年大鼠脑损伤过程中神经细胞凋亡及凋亡诱导因子(AIF)的表达情况。方法:免疫组织化学技术检测脑组织的AIF表达情况,TUNEL法检测神经细胞凋亡数。结果:与NS对照组相比,LPS组脑组织AIF蛋白表达及神经细胞凋亡增多,差异有统计学意义(P＜0.01)。结论:凋亡参与了LPS致脑损伤的发生发展过程。AIF表达增加可能是导致神经细胞凋亡的原因之一。第三部分肝细胞生长因子对脂多糖致幼年大鼠感染性脑损伤的保护作用目的:探讨肝细胞生长因子(HGF)对脂多糖致幼年大鼠感染性脑损伤的保护作用。方法:经大鼠颈外动脉注射LPS后即刻注射HGF,观察脑组织EB含量、GFAP、NSE、AIF蛋白表达量,以及神经细胞凋亡数。结果:HGF组各时间点脑组织EB含量、NSE、GFAP、AIF蛋白表达水平低于LPS组(P＜0.01)。结论:早期应用肝细胞生长因子对LPS致幼年大鼠脑损伤具有保护作用。第四部分褪黑素在LPS致幼年大鼠脑损伤中的保护作用目的:探讨褪黑素在LPS致脑损伤中的保护作用。方法:应用LPS经大鼠颈外动脉注射,分别提前及同时腹腔注射MT,观察脑组织EB含量、GFAP、NSE、AIF蛋白表达量,以及神经细胞凋亡数。结果:MT保护组24h、48h时间点脑组织EB含量、NSE、AIF、GFAP蛋白及凋亡表达变化均低于LPS组(P＜0.05),提前组和0小时组相比无统计学意义(P＞0.05)。结论:MT对LPS致幼年大鼠脑损伤具有保护作用,可能与其降低凋亡诱导因子AIF的表达,减少神经细胞凋亡有关,与抗生素同时应用即可起到保护作用。
[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.
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2008
【分类号】：R-332;R741

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