基于Hedgehog信号通路探讨“肾虚血瘀”骨代谢失常的分子机制

Kidney deficiency and blood stasis caused bone metabolism disorders seen in diseases such as osteoporosis, Hedgehog signaling pathway is closely related to bone metabolism is known, and kidney invigorate the circulation of TCM clinical treatment of osteoporosis, bone metabolism is curative effect . This study intends to solve the key scientific problem is "the kidney and blood stasis" metabolic disorder of bone disease osteoporosis, for the sample, clarify "kidney deficiency blood stasis" is one of the molecular mechanism of bone metabolism disorders may be related to hedgehog signaling pathways critical gene and protein, And kidney invigorate the circulation of Chinese traditional medicine compound can be achieved by adjusting the Hedgehog signaling pathway and the role of the treatment of osteoporosis .The research is divided into two parts in vivo and in vitro experiments, to the ovary osteoporosis model rats and osteoblast as the object of experimental research , as a whole, organ, cell and molecular level . Compare fill kidney essence, promoting blood circulation to remove blood stasis, kidney invigorate the circulation of Chinese traditional medicine compound for ovarian of bone metabolism in rat models of osteoporosis prevention and treatment effect and its influence to the Hedgehog signaling pathway related gene expression. To clarify tonifying kidney, activating blood and kidney invigorate the different disorders of the TCM compound on bone metabolism of osteoporosis prevention and cure function and molecular mechanism for clinical prevention and treatment of osteoporosis to provide the best treatment.

"肾虚血瘀"骨代谢失常可见于骨质疏松症等疾病，已知hedgehog信号通路与骨代谢密切相关，补肾活血中药临床上治疗骨质疏松症，调整骨代谢疗效确切。本研究拟解决的关键科学问题是以"肾虚血瘀"骨代谢失常疾病骨质疏松症为示例，阐明"肾虚血瘀"骨代谢失常的分子机制之一可能与hedgehog信号通路关键基因、蛋白密切相关，而补肾活血中药复方可以通过调整Hedgehog信号通路而达到治疗骨质疏松症的作用。研究分为体内和体外实验两个部分，以去卵巢骨质疏松症模型大鼠和成骨细胞为实验研究对象，从整体、器官、细胞、分子水平，比较补肾填精、活血化瘀、补肾活血中药复方对去卵巢骨质疏松症模型大鼠骨代谢的防治作用以及对Hedgehog信号通路相关基因表达的影响，阐明补肾、活血、补肾活血不同中药复方对骨质疏松症骨代谢失常的防治作用以及分子机制，为临床上防治骨质疏松症提供最佳的中医药治疗方案及其机理提供实验依据。

“随着生命科学的飞速发展，中国已经全面进入老龄化社会。据国家统计局调查，2014年末，我国60周岁及以上人口为2.12亿人，占总人口比重的15.5%；65周岁及以上人口为1.37亿人，占10.1%。老龄社会将要面对的最棘手问题之一就是骨质疏松症。目前骨质疏松症的发病率逐年上升，严重影响人类的生命和健康，如何有效的防治骨质疏松症已是目前人类关注的焦点。中医药防治骨质疏松症有悠久的历史及丰富经验，本研究以去卵巢骨质疏松症模型大鼠和成骨细胞为实验研究对象，比较补肾填精、活血化瘀、补肾活血中药复方对去卵巢骨质疏松症模型大鼠骨代谢的防治作用以及对Hedgehog信号通路相关基因表达的影响。研究结果表明：骨质疏松症大鼠骨组织、肾组织和血清中Hedgehog信号通路相关蛋白Sonic Hh (Shh)、Indian Hh (IHh)、Ptch1、核转录因子Gli1、Gli3、蛋白激酶A （PKA）、血管内皮生长因子（VEGF）、血管形成素（Ang-1）及mRNA表达量有显著改变，提示Hedgehog信号通路相关因子的变化与骨质疏松症的发生密切相关，这可能是骨质疏松症的病理机制之一。运用补肾、活血中药复方干预后，各组蛋白含量及mRNA表达量有不同程度的改变。综上所述，“肾虚血瘀”骨代谢失常与Hedgehog信号通路相关因子密切相关，通过补肾、活血法可以改善变化表达水平可能是补肾、活血中药复方治疗骨质疏松症的作用机制之一。