内毒素休克大鼠脑损伤的分子机制及人参二醇组皂苷对其影响的实验研究

发布时间：2018-02-16 08:57

本文关键词： 内毒素内毒素休克脑损伤信号转导核因子κB 谷氨酸转运体人参二醇组皂苷地塞米松　出处：《吉林大学》2005年博士论文　论文类型：学位论文

【摘要】：通过复制大鼠内毒素休克模型,探讨内毒素引起脑损伤的分子机制,同时对比观察了人参二醇组皂苷(PDS)与地塞米松(Dex)对其的影响。主要研究发现,内毒素休克时,大鼠脑皮质CD14、TLR4/TLR2表达增加;采用电泳迁移率改变分析(EMSA)检测脑皮质转录因子NF-κB的DNA结合活性,结果显示休克后1h和4h NF-κB的DNA结合活性增高,且以1h增高明显。脑组织中特有的谷氨酸转运体表达减少(EAAT2和EAAT3),也参与了内毒素休克脑损伤。所以,可以认为脑组织细胞与其它细胞一样,NF-κB在炎症反应的早期被激活,随即诱导IL-18等细胞因子、NOS等的产生,引起脑组织损伤。谷氨酸转运体表达下降和自由基的生成、NO的大量释放存在着联系,亦可能与给予LPS后激活了NF-κB有关。本研究发现PDS 具有改善内毒素休克大鼠血液动力学、流变学和抗氧化损伤作用;还可降低脑细胞CD14、TLR4/TLR2 的表达。我们采用EMSA实验首次证实PDS 可明显抑制NF-κB 的DNA 结合活性,从而减少细胞因子的产生。与Dex 相比,PDS 通过影响脑细胞内毒素信号转导途径的多个环节,具有多靶点细胞保护作用。
[Abstract]:By copying the model of endotoxic shock rats, to investigate the molecular mechanism of brain injury induced by endotoxin, and compared the effects of Panaxadiol Saponins (PDS) and dexamethasone (Dex) on it. The main study found that during endotoxic shock, cerebral cortex of rats CD14, TLR4/TLR2 expression increased; the electrophoretic mobility shift assay (EMSA detection of cerebral cortex) NF- transcription factor kappa B binding activity of DNA, 1H and 4H results showed that the shock NF- kappa B binding activity of DNA increased, and 1H increased significantly. The unique brain tissues decreased expression of glutamate transporters (EAAT2 and EAAT3), is also involved in endotoxic shock and brain damage. Therefore, the brain can think tissue cells and other cells, NF- kappa B at the early stage of inflammation is activated, then induced by cytokines such as IL-18, NOS etc., caused by brain injury. Expression of glutamate transporters decreased and free radical generation, NO A large amount of release has a connection and may also be associated with the activation of NF- kappa B after LPS.
The study found that PDS can improve the hemodynamics of rats with endotoxic shock, rheology and anti oxidative effect; also can reduce the CD14 of brain cells, the expression of TLR4/TLR2 by EMSA. We experimentally confirmed PDS could inhibit NF- kappa B binding activity of DNA, thus reducing the production of cytokines. Compared with Dex, PDS by the impact of a number of link the brain cells endotoxin signal transduction pathway, with cell protective effect of multiple targets.

【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R363;R285

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