VEGF基因转染BMSCs移植对薄型子宫内膜大鼠模型的治疗作用及机制研究

The endometrial receptivity is seriously impaired in thin endometrium, leading to embryo implantation failure and infertility. So far, there is no effective treatment. The low expression of endometrial vascular endothelial cell growth factor (VEGF) and increased basilar artery blood flow resistance play key roles in the pathogenesis of thin endometrium, leading to the dysplasia of gland epithelial eventually. Our preliminary study demonstrated that transplantation with bone marrow mesenchymal stem cells (BMSCs) could effectively promote the growth of thin endometrium, and improve endometrial receptivity. Based on our previous study, we suggest BMSCs transfected with VEGF gene as the novel treatment of thin endometrium after examining the expression of VEGF in vitro. The therapeutic effective of VEGF transfected BMSCs on thin endometrium was observed by evaluating the endometrial regeneration and receptivity and the molecular mechanism for the effect was investigated via Real-time tracking transplanted BMSCs, and detecting the expression of VEGF on RNA and protein levels. This concept and the research detail mentioned above cannot be found in the open literature by now. The implementation of this study is of theoretic and realistic significance. It can not only enrich theory in the field of the gene therapy, but also lay the foundation for the gene therapy of thin endometrium.

薄型子宫内膜严重削弱内膜容受性，导致胚胎着床失败而不孕，目前尚无有效的治疗方法。其病理基础是子宫内膜血管内皮细胞生长因子（VEGF）低表达，基底动脉血流阻力增高，最终导致腺上皮发育不良。申请人前期研究发现骨髓间充质干细胞（BMSCs）移植能有效促进薄型子宫内膜的生长，改善子宫内膜容受性。为在前期基础上进一步提高治疗效果，本项目提出VEGF基因转染的BMSC移植治疗薄型子宫内膜的新方法，拟将VEGF基因转染至BMSCs，体外验证VEGF的表达后，移植转染后的BMSCs至薄型子宫内膜模型大鼠体内，观察表达VEGF的BMSCs移植对薄型子宫内膜及其容受性的影响；并实时追踪移植细胞，及从RNA和蛋白水平检测VEGF表达，探索其改善薄型子宫内膜的分子机制。以上研究思想和研究内容目前国内外均无报道。本项目的成功，不仅可丰富基因治疗理论，还为基因治疗在薄型子宫内膜的临床应用奠定基础，具有理论和现实意义。

薄型子宫内膜严重削弱内膜容受性，导致胚胎着床失败而不孕，目前尚无有效的治疗方法。其病理基础是子宫内膜血管内皮细胞生长因子（VEGF）低表达，基底动脉血流阻力增高，最终导致腺上皮发育不良。本人前期研究发现骨髓间充质干细胞（BMSCs）移植能有效促进薄型子宫内膜的生长，改善子宫内膜容受性。为在前期基础上进一步提高治疗效果，本项目提出VEGF基因转染的BMSC移植治疗薄型子宫内膜的新方法，拟将VEGF基因转染至BMSCs，体外验证VEGF的表达后，移植转染后的BMSCs至薄型子宫内膜模型大鼠体内，观察表达VEGF的BMSCs移植对薄型子宫内膜及其容受性的影响；并实时追踪移植细胞，及从RNA和蛋白水平检测VEGF表达，探索其改善薄型子宫内膜的分子机制。以上研究思想和研究内容目前国内外均无报道。本项目的成功，不仅可丰富基因治疗理论，还为基因治疗在薄型子宫内膜的临床应用奠定基础，具有理论和现实意义。