Ghrelin/NF-κB介导的巨噬细胞与髓核细胞交互作用机制及其对椎间盘退变的影响

A large number of studies show that the relationship between Ghrelin and the inflammatory response is more closely. It is well known that chronic inflammation plays an important role in the process of disc degeneration. Our preliminary experiment showed that Ghrelin reduced significantly in degenerative intervertebral disc tissue specimens, and exogenous Ghrelin can effectively alleviate the degeneration of nucleus pulposus cells. This project focuses the lumbar disc degeneration and pathological microenvironment, combined with our previous research results, analyzes Ghrelin/NF-κB signal pathway in intervertebral disc inflammation infiltration of macrophages and polar transformation, molecular mechanism of interaction and regulation between and macrophages and nucleus pulposus, discusses the activation of Ghrelin expression and inhibition of NF-κB activity could improve the lumbar intervertebral disc degeneration. The related research about Ghrelin and disc degeneration has not been reported yet.The mechanism of abnormal regulation of will help to clarify the Ghrelin/NF-κB signaling pathway in macrophages in intervertebral disc degeneration, understand the regulation of inflammatory cells and pathological tissue of lumbar degenerative disease in the micro environment. This study will provide a solid and reliable support for preventing and treatment of intervertebral disc degenerative disease .

大量研究表明Ghrelin与炎症反应之间关系密切，而慢性炎症一直在椎间盘退变过程中发挥着重要的作用。我们的前期研究发现Ghrelin含量在退变椎间盘标本中显著降低，而外源加入Ghrelin则有效缓解髓核细胞株的退变。本项目围绕椎间盘退变和病理微环境这一热点，结合我们的前期研究，拟分析Ghrelin/NF-κB信号通路介导的椎间盘退变过程中巨噬细胞的浸润和极性转化，及巨噬细胞与髓核细胞之间相互影响和调控作用的分子机制，探讨靶向激活Ghrelin的表达，抑制NF-κB的活性，对于椎间盘退变改善的效果。目前国内外对于Ghrelin与椎间盘退变关系的相关研究，尚未见报道。本研究的完成将有助于阐明巨噬细胞中Ghrelin/NF-κB信号通路的异常调控在椎间盘退变中发挥的重要功能，了解疾病微环境中炎症细胞与病变组织细胞相互诱导和调控机制，为椎间盘退行性疾病的防治奠定坚实可靠的理论基础和实验保证。

本项目基本参照项目计划书完成，未有大的研究内容调整。经本项目的研究，我们明确了Ghrelin/NF-κB信号通路作用于巨噬细胞极化，以及巨噬细胞双向极化在正常和退变的腰间盘组织中的功能和分子调控网络。通过各项细胞学和组织学检测，我们理解了病变组织中Ghrelin的调控异常如何影响微环境中巨噬细胞和髓核细胞正常生理功能。同时本项目阐明了炎症微环境中椎间盘退变组织与巨噬细胞之间的相互诱导和活化机制。最后我们利用Ghrelin或其受体激活剂，抑制NF-kB的激活，重塑椎间盘组织炎症微环境，证明了其对于改善或逆转椎间盘退变的可行性。