青少年特发性脊柱侧凸患者可溶性瘦素受体水平异常及其上游调控机制相关研究

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity, which is characterized as abnormal growth and development of the body， including lower body mass index （BMI）, lower bone mineral density （BMD）, and higher corrected height. The above abnormal characteristics indicated that the abnormal leptin bioavailability may contribute to the development and progression of AIS. We previously reported that the bioavailability of the circulating leptin was significantly lower in a small sample of AIS patients when compared with those in normal adolescents. Integrating the leptin metabolism and regulation paths, we hypothesized that the abnormal leptin bioavailability may play an important role in the development and progression of AIS, while the soluble leptin receptor abnormality is the sole factor that could influence the leptin bioavailability, thus, we plan to identify whether there are abnormalities of soluble leptin receptor level and leptin bioavailability in AIS patients, via investigating the concentration of soluble leptin receptor in a large population of AIS patients. In addition, as the soluble leptin receptor is generated by that the membrane leptin receptor sheds off and dissolves in blood. Therefore, we plan to investigate the polymorphism of leptin receptor gene in AIS patients and to culture a cell line that overexpresses leptin receptor, in order to identify the relevant soluble-leptin-receptor-genesis proteinase, and to study the upstream regulation mechanism of the soluble leptin receptor abnormality in AIS patients, which in turn can further elucidate the relationship between this abnormality and the etiology of AIS.

青少年特发性脊柱侧凸（AIS）是最常见脊柱畸形，常具有异常生长发育特征：体型消瘦、低骨密度及较高校正身高。上述异常提示瘦素生物度异常可能在AIS发生发展中起重要作用。之前本课题组首次在小样本AIS女孩中发现外周血瘦素生物利用度明显低于同龄健康女孩。结合瘦素代谢和调节路径，本研究提出：异常瘦素生物利用度可能在AIS发生发展中起关键作用，而可溶性瘦素受体(sOB-R)水平异常又是影响瘦素生物利用度的核心，因此本研究计划通过研究大样本AIS患者中sOB-R浓度以证实AIS患者sOB-R水平及瘦素生物利用度是否存在异常。此外，由于sOB-R水平受瘦素受体基因多态性调控且是由细胞膜上瘦素受体脱落溶于血中形成，因此我们将分别通过研究AIS患者瘦素受体基因多态性以及建立瘦素受体高表达细胞株，寻找可溶性瘦素受体生成相关蛋白酶并研究AIS患者sOB-R异常上游调控机制，从而进一步阐明其与AIS病因学的关系。

青少年特发性脊柱侧凸（AIS）是最常见脊柱畸形，具有异常生长发育特征：体型消瘦、低骨密度及较高校正身高。上述异常提示瘦素生物度异常可能在AIS 发生发展中起重要作用。之前本课题组首次在小样本AIS 女孩中发现外周血瘦素生物利用度明显低于同龄健康女孩。结合瘦素代谢和调节路径，本研究证实：异常瘦素生物利用度可能在AIS 发生发展中起关键作用，而可溶性瘦素受体(sOB-R)水平异常又是影响瘦素生物利用度的核心，因此本研究计划通过研究大样本AIS 患者中sOB-R 浓度证实LRAIS 患者sOB-R 水平及瘦素生物利用度是否存在异常。此外，由于sOB-R 水平受瘦素受体基因多态性调控且是由细胞膜上瘦素受体脱落溶于血中形成，因此我们将分别通过研究AIS 患者瘦素受体基因多态性以及建立瘦素受体高表达细胞株，找出了可溶性瘦素受体生成相关蛋白酶并研究AIS 患者sOB-R 异常上游调控机制，从而进一步阐明了其与AIS 病因学的关系。