MicroRNA在孕期低氧致先天性脊柱侧凸发生发展中的作用及机制

The sophisticated interaction of environmental and genetic factors is thought to be the pathogenesis resulting congenital scoliosis(CS). Environmental factor in embryo may play an important role in the onset of CS, but the mechanism was unclear. Hypoxia during pregnant theoretically may cause CS.In the previous study, we have found that hypoxia during pregnant can induce congenital scoliosis. However, the molecular mechanism underlining its pathogenes is not well known. We used miRNA-Chip to analysis the miRNA which were were significantly higher or lower in CS than the normal one. Therefore, the techniques of siRNA gene knock-in and gene knock-out will be used to detect the mechanism of appearance between the CS and the normal one in this study. And verification of the difference will be conducted through the patients. According to individual-group and globe-cell-animal model studies, we plan to find the related noncoding RNA for the genesis and prognosis of CS. This study will give a new insight into the pathogenesis of CS and provide a new way for the early diagnosis, treatment and prevention of CS.

先天性脊柱侧凸(CS)的诊治是脊柱外科的难题，其发生除与遗传因素相关外,环境因素也发挥重要作用，但具体病因和机制尚不明确。近来发育学研究提示孕期低氧可能在CS发生发展过程中起重要作用。前期的研究中，我们证实孕期低氧能导致CS的发生，但其具体机制尚不明确。我们推测microRNA可能调控孕期低氧致CS的发生发展。为证明此假说，本课题将应用miRNA芯片筛选出调控孕期低氧致CS发生相关的miRNA；进一步应用siRNA、基因敲入、基因敲除等技术在细胞水平、动物模型中进行基因表达调控和功能的验证，从动物模型－环境因素－非编码RNA－病例多个层次，寻找和阐明调控孕期低氧致CS发病相关的分子机制。目前国内外尚未见CS环境因素－非编码RNA研究的报道，本研究将为CS的预防、早期诊治提供新的思路和新的靶点。

先天性脊柱侧凸(CS)的诊治是脊柱外科的难题，其发生除与遗传因素相关外,环境因素也发挥重要作用，但具体病因和机制尚不明确。近来发育学研究提示孕期低氧可能在CS发生发展过程中起重要作用。前期的研究中，我们证实孕期低氧能导致CS的发生，但其具体机制尚不明确。我们推测microRNA可能调控孕期低氧致CS的发生发展。为证明此假说，本课题将应用miRNA芯片筛选出调控孕期低氧致CS发生相关的miRNA；进一步应用siRNA、基因敲入、基因敲除等技术在细胞水平、动物模型中进行基因表达调控和功能的验证，从动物模型－环境因素－非编码RNA－病例多个层次，寻找和阐明调控孕期低氧致CS发病相关的分子机制。本课题通过动物模型筛选出表达差异的miR-a,并在细胞模型进行了验证,证实了其可能在先天性脊柱侧凸发生发展中起重要作用.目前国内外尚未见CS环境因素－非编码RNA研究的报道，本研究将为CS的预防、早期诊治提供新的思路和新的靶点。