血管生成是提高子宫内膜容受性的重要环节，转录因子KLF4在血管生成中具有重要作用。前期研究证实补肾法具有上调VEGF、促进子宫内膜血管生成、改善子宫内膜容受性的作用。预实验结果显示，补肾调经方和VEGF在子宫内膜微血管内皮细胞可上调KLF4表达。因此我们推测，补肾法可能诱导KLF4-VEGF形成反馈环路促进子宫内膜血管生成。本项目拟建立细胞模型，用过表达KLF4和特异性敲低KLF4的病毒感染子宫内膜微血管内皮细胞，研究KLF4在子宫内膜血管生成中的作用；探讨补肾法诱导KLF4与VEGF形成反馈环路调控血管生成的机制。在整体水平过表达或敲低KLF4，建立降低子宫内膜容受性的控制性超促排卵小鼠模型并给予补肾干预，采用免疫双荧光染色观察KLF4在子宫内膜微血管中的表达探讨KLF4在补肾法促血管生成中的作用机制。这对于揭示中医“肾主生殖”的理论内涵，探索中医调经种子的作用机制具有重要意义。

The transcription factor KLF4 plays an important role in angiogenesis which can improve endometrial receptivity. Previous studies have demonstrated that kidney-tonifying method could up-regulate VEGF expression, facilitate endometrial angiogenesis and improve endometrial receptivity. Our study indicated that KLF4 expression was induced by the kidney-tonifying method and VEGF. Therefore, we speculate that kidney-tonifying method may induce KLF4-VEGF feedback loop formation, subsequently leading to endometrial angiogenesis. The project intends to study whether KLF4 could regulate endometrial angiogenesis and the mechanism by which the kidney-tonifying method induce the KLF4-VEGF feedback loop formation to regulate the endometrial angiogenesis at the cellular level. In addition, we will establish an animal model with decreasing endometrial receptivity by controlled ovarian hyperstimulation. Treated with the kidney-tonifying method, we aim to observe KLF4 expression in endometrial microvasculature by double immunofluorescence staining, and study the effect of KLF4 overexpression or knockdown on expression of VEGF in endometrium which induced by kidney-tonifying method. This study have significant implications for illuminating the theory of “kidney dominating reproduction” and exploring the mechanism of traditional Chinese medicine in improving reproduction.