瘦素引起腰椎间盘髓核退变的机制研究

Lumbar disc degeneration (LDD) is the most common etiology behind non musculoskeletal low back pain. Obesity is possibly an important factor contributory to LDD development, but its mechanism is not clear.In obese patients, serum Leptin have been demonstrated to be significantly higher in preliminary studies. We found that Leptin can stimulate cell proliferation and the regulation of lumbar nucleus pulposus cellular cytoskeleton remodeling. We also discovered that the RhoA / ROCK signaling pathway increased Cofilin protein expression. We speculate that the JAK / STAT and ERK signaling pathways mediated by the proliferation of nucleus pulposus cells and cells of the RhoA / ROCK signaling pathway mediated cytoskeletal protein remodeling, which leads to the development of LDD.To prove this hypothesis, we employed the experimental application of fluorescence resonance energy transfer technology, real-time PCR, Western blot , MRI and other techniques. Using animal models and cell two levels we tracked Leptin and its signaling pathway. This helped to clarify the relationship between obesity, Leptin and LDD development via this unique signal transduction pathway.Our observation suggests that obesity prevention and treatment may affect LDD - this may pave a new thinking and spur the development of new drug targets.

腰椎间盘退行性变(LDD)是引起下腰疼最常见的病因。肥胖是影响腰LDD发生、发展的重要因素，但其机制尚不明确。肥胖症血清的瘦素水平显著增高，前期研究中，我们发现瘦素能激活JAK/STAT和ERK信号途径刺激腰椎髓核细胞增殖而抑制这些信号途径后这种效应并不能完全抑制。还发现瘦素调控腰椎髓核细胞的细胞骨架重塑，并检测到Cofilin蛋白表达增高。我们推测瘦素是通过细胞外基质激活RhoA/ROCK信号通路引起细胞骨架蛋白重塑。为证明这种假说，本实验应用荧光共振能量转移技术、siRNA技术等技术，观察瘦素以及其介导的信号通路对腰椎间盘细胞外基质、骨架蛋白的影响，从而阐明瘦素及其调控的miRNA与LDD发生发展的关系及其机制，并为肥肥胖引起的IDD的防治提供一种新思路和药物作用新靶点。

腰椎间盘退行性变(LDD)是引起下腰疼最常见的病因。肥胖是影响LDD发生、发展的重要因素，但其机制尚不明确。肥胖症血清的瘦素水平显著增高，前期研究中，我们发现瘦素能激活JAK/STAT和ERK信号途径刺激腰椎髓核细胞增殖而抑制这些信号途径后这种效应并不能完全抑制。还发现瘦素调控腰椎髓核细胞的细胞骨架重塑，并检测到Cofilin蛋白表达增高。在此项研究中，我们应用荧光共振能量转移技术、siRNA技术、miRNA芯片等技术，观察瘦素以及其介导的信号通路对腰椎间盘细胞外基质、骨架蛋白、miRNA的影响，证实了瘦素是通过激活RhoA/ROCK信号通路引起细胞骨架蛋白重塑，miRNA也在瘦素刺激髓核细胞增殖、细胞外基质变化、骨架蛋白重塑中起调控作用。阐明了瘦素及其调控的miRNA与LDD发生、发展的关系及其机制，并为肥胖引起的LDD的防治提供一种新思路和药物作用新靶点。