基于TGF-β/SMADs信号通路研究护卵汤对POR模型大鼠卵巢反应性的影响

Poor/low ovarian response (POR) is one of the urgent problem in the controlled ovarian hyperstimulation(COH) of modern assisted reproductive technology(ART), which especially caused by premature ovarian failure (POF). These patients are difficult to obtain desired results in COH who had to choose for donated oocytes or give up. TCM therapy for infertility is considerable evidence that the unique advantages of TCM therapy for ovarian dysfunction (ovulation obstructive barrenness), which can especially promote the ovarian response to gonadotropin(Gn), but the mechanism is not clear. The preliminary studies on Huluantang showed that improvement of ovarian response in rats under GnRHa controlled ovarian hyperstimulation,and screening TGF-β1 and other cytokines in ovary associated with ovarian response by antibody array. The first target in this study is to establish Animal Model of POR, then the effects of Huluantang upon the ovarian response in rats of POR will be observed in recruitment, selection and dominance of follicular development. TGF-β/SMADs signal pathway is selected to explore molecular mechanism of action on POR of Huluantang according to the preliminary findings. Through this study on Huluantang in rats of POR which include multi-stage and multi-target, we expect to provide objective and scientific experimental basis for Huluantang applying to POR in clinical COH, and one new idea for integrated traditional chinese and western medicine in the clinical application.

卵巢反应不良（POR）是现代辅助生殖超排卵技术中迫切需要解决的难题之一，特别是早期卵巢功能衰退引起的POR患者，常因超排卵难以获得理想结果，不得不选择供卵治疗或放弃。中医药治疗卵巢功能障碍相关疾病具有独特优势和肯定疗效，特别是能提高卵巢对促性腺激素的反应性进而改善卵巢功能，但作用机制尚未明确。我们的前期研究发现护卵汤能改善超排卵大鼠的卵巢反应性，并通过抗体芯片筛选出相关因子TGF-β1等。本研究拟在前期工作基础上首先建立POR动物模型，然后观察护卵汤在卵泡募集及卵泡发育的不同阶段对POR模型大鼠卵巢反应性的影响，并根据前期结果选择TGF-β/SMADs信号通路为切入点，探讨护卵汤对POR模型大鼠卵巢反应性的作用靶点及分子作用机制。通过开展护卵汤对POR模型多阶段多靶点的研究，期望为护卵汤临床干预POR提供科学客观的实验依据，为中西医结合在临床的应用提供新的思路。

卵巢反应不良（POR）是现代辅助生殖超排卵技术中迫切需要解决的难题之一，特别是早期卵巢功能衰退引起的POR患者，常因超排卵难以获得理想结果，不得不选择供卵治疗或放弃。中医药治疗卵巢功能障碍相关疾病具有独特优势和肯定疗效，特别是能提高卵巢对促性腺激素的反应性从而改善卵巢功能，但作用机制尚未明确。本研究在前期工作基础上，通过慢性制动应激建立POR小鼠模型，观察并发现护卵汤对POR小鼠卵泡募集及成熟阶段各级卵泡构成比例并无显著影响，但在与卵巢反应性密切相关的TGF-β/ Smads信号通路中，发现护卵汤能上调POR小鼠卵巢TGF-β1、P-Smad3和FSHR蛋白/核酸的表达，在分子层面验证了中药护卵汤多靶点干预POR的作用机制。此外，研究发现护卵汤还能促进多周期促排卵小鼠的子宫内膜生长发育及ER/PR蛋白表达。本项目研究成果证实在现代辅助生殖技术中，中药护卵汤的应用对改善卵巢反应性和子宫内膜容受性具有积极作用，为中西医结合在临床的应用提供更多的实验依据和思路。