TSLP介导JAK1/Akt信号通路在腰椎间盘退变突出过程中的作用及其机制研究

项目名称： TSLP介导JAK1/Akt信号通路在腰椎间盘退变突出过程中的作用及其机制研究

项目编号： No.81460332

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 祝勇

作者单位： 内蒙古医科大学

项目金额： 47万元

中文摘要： 椎间盘退变是腰腿痛的主要原因，研究退变的发生发展机制已成为当今的热点。在引起退变的众多因素中，髓核细胞凋亡是最重要的原因之一。那么机体有没有自身的调节机制来遏制退变的发展呢？我们的前期研究显示：当椎间盘退变突出后，TNF-a/NF-кB高表达产生TSLP，后者具有促进突出的髓核重吸收的作用。进一步研究发现：阻断Akt通路可以明显抑制重吸收因子的表达。因TSLP与IL-7样受体结合，激活JAK1/Akt信号通路，调节下游因子的转录，我们推测TSLP通过JAK1/Akt通路介导了髓核突出重吸收。X连锁凋亡抑制蛋白（XIAP）是在人体各组织中广泛存在的抑制细胞凋亡蛋白，其活化受到上游Akt通路的调控。我们推断在髓核突出后，椎间盘自身的稳态被打破，在发生炎症反应的同时,通过TSLP激活JAK1/Akt通路，除了促进突出的髓核重吸收外，还上调XIAP的表达来抑制了髓核细胞的凋亡，延缓椎间盘的退变。

中文关键词： 胸腺基质淋巴生成素；信号通路；椎间盘突出；退变

英文摘要： Intervertebral disc degeneration is one of the most important causes of lumbocrural pain. The underlying mechanism of intervertebral disc degeneration is on the resent research point. Among numerous degeneration inducible factors, nucleus pulposus cell apoptosis plays the most critical role. However, is there a per se regulation mechanism to prevent the progression? Our previous data indicated that after the protrusion of intervertebral disc, TSLP expression was increased by activated TNF-a/ NF-кB pathway which is responsible for the reabsorption of protruded nucleus pulposus. Further investigation revealed that the expression of reabsorption-associated factors eliminated by blockade of Akt pathway. Since JAK1/Akt pathway is activated by TSLP and its binding to IL-7 like receptors, thus regulate the transcription of downstream substrates. We hypothesize that TSLP can regulate nucleus pulposus reabsorption via JAK1/Akt pathway. X-linked inhibitor-of-apoptosis protein(XIAP) is a widely distrubited anti-apoptotic molecule which is activated by Akt. In the condition of nucleus pulposus protrusion, the environment balance in intervertebral disc is disrupted and inflammatory response is triggered. We suspect that in such condition TSLP activates JAK1/Akt pathway, as a consequence it not only promotes the reabsorption of nucleus pulposus, but also elevates XIAP expression to inhibit nucleus pulposus cell apoptosis, both of which postpone intervertebral disc degeneration progression.

英文关键词： TSLP;singal pathway;herniated intervertebral disc;degeneration