神经生长因子在子宫腺肌病患者内膜容受性受损中的作用及调控机制

Adenomyosis (AM) patients have a high incidence of infertility, and lower pregnancy rates in assisted reproduction population. Defective endometrial receptivity is the main reason for subfertility, but specific mechanism is unknown. The protein level of nerve growth factor (NGF) was high in AM lesions, playing a role of aggravating inflammation and inducing innervation. Our previous studies have shown that NGF can promote the proliferation of human AM endometrial stromal cell in vitro culture, raising aromatase expression; Using AM antagonism in mice model NGF can raise the gene HOXA10, down regulating aromatase and inflammatory factor receptors expression. Then we speculate that NGF plays a role in the mechanism of endometrial receptivity damage in AM patients.We have to do in-vitro cell culture experiments first in this research. SiRNA transfection, NGF gene over expression and other techniques will be used to study the aromatase related estrogen synthesis and signal transduction mechanisms. Then we will feed mice which have AM and receive anti-NGF therapy. The depth and area of AM nodules will be calculated. Mean while, inflammatory cytokines, receptivity related cytokines and pregnancy rate after embryo transfer will by examined. All the above were used to explain the mechanism of AM endometrial receptivity defection and assess the value of anti-NGF using in AM therapy.

子宫腺肌病(AM)在不孕人群发病率高，在助孕人群妊娠率低，子宫内膜容受性损伤是AM不孕的主要原因，但机制不详。神经生长因子(NGF)在AM病灶与在位内膜高表达，发挥加剧炎症反应、诱导神经植入的作用。我们前期研究表明NGF可促进人AM内膜间质细胞增殖，上调芳香化酶表达；AM小鼠拮抗NGF可上调内膜容受性标志物 HOXA10、下调芳香化酶及炎症因子受体表达。由此推测NGF通过调节芳香化酶表达影响子宫雌激素水平，在AM患者内膜容受性受损机制中发挥调控作用。本课题首先培养AM患者内膜间质细胞与腺上皮细胞，通过siRNA转染、基因过表达等方法研究NGF对这两种细胞雌激素合成、雌孕激素受体的调节作用及其信号转导机制；其次给予AM小鼠抗NGF抗体，评估其对病灶增殖、子宫炎症、容受性相关因子表达及鼠胚移植后妊娠率变化的作用。本研究将进一步阐明AM内膜容受性受损的分子机制，以期寻找新生物学靶点，指导临床治疗