补肾活血方及其有效药物血清基于TLR4/NF-κB通路对复发性流产的调控机制

In this study, using RT-PCR,Westernblotting,serum pharmacology method, both from experimental and clinical aspects, following the guidance of tonifying kidney and promoting blood circulation method, clarify regulating mechanism of tonifying kidney and promoting blood circulation decoction on ACA ( + ) caused RSA based on TLR4/NF-kB pathway.And in this study, based on previous work, using the method of serum pharmacology, treat ACA ( + )RSA human decidual cells with effective drugs serum of tonifying kidney and promoting blood circulation decoction and cryptotanshinone , to further clarify the transmission mechanism of TLR4/NF-kB pathway in ACA ( + ) caused RSA.Lay the foundation for tonifying kidney and promoting blood circulation decoction and traditional Chinese medicine monomer in the clinical on the cytokine signaling pathway.

本研究采用RT-PCR、Westernblotting、血清药理学等方法，从实验及临床两方面阐明补肾活血法指导下，补肾活血方对ACA(+)致RSA TLR4/NF-kB通路调节机制；在本研究前期工作基础上，采用血清药理学方法，予补肾活血方有效组分药物血清及隐丹参酮单体对ACA(+)RSA人体外蜕膜细胞干预，进一步明确 TLR4/NF-kB通路在ACA(+)致RSA中传导机制，从细胞因子信号传导通路方面，为补肾活血方及中药单体在本病的临床使用奠定基础。

抗心磷脂抗体（ACA）阳性可以导致复发性流产（RSA）的发生，其机制为：ACA识别β2GPⅠ/anti- β2GPⅠ抗体并形成复合物，通过TLR4/NF-κB通路，调控通路下游因子肿瘤坏死因子α (TNF-α)、环氧化酶2（COX-2）及前列腺素类分子（PGs）等细胞因子水平，从而导致胚胎异常而引起病理妊娠，最终导致流产。本研究从实验及临床两方面阐述补肾活血法指导下，补肾活血方对ACA（+）致RSA TLR4/NF-κB通路调节机制。同时予补肾活血方有效组分药物血清及隐丹参酮单体对ACA（+）RSA人体外蜕膜细胞干预，进一步明确TLR4/NF-κB通路在ACA（+）致RSA的传导机制。结果表明：1、ACA阳性可以通过 TLR4/NF-κB信号通路导致RSA。2、补肾活血方可通过调节TLR4/NF-κB信号传导通路相关细胞因子的表达，抑制该通路过度表达，最终达到补肾活血，祛瘀安胎的目的。3、肾虚血瘀型ACA（+）RSA早期难免流产和正常早期妊娠的流产蜕膜基因存在着显著差异。4、补肾活血方、隐丹参酮及阿司匹林都能够治疗肾虚血瘀型ACA（+）RSA，但补肾活血方的治疗效果最好。这些研究为补肾活血方及中药单体在本病的临床应用奠定了基础。