补肾活血方及有效组分对抗心磷脂抗体阳性复发性流产蜕膜基质细胞TLR4/NF-κB/COX-2通路的影响  

Effects of Bushen Huoxue Decoction and its effective components on TLR4/NF-κB/COX-2 pathway of decidual stromal cells in recurrent spontaneous abortion with positive cardiolipin antibody

作　　者：赵小萱 冯晓玲[2] 周旋[1] 郭鲁秦 李娜[2] 张杨[2] 赵颜[2] ZHAO Xiao-xuan;FENG Xiao-ling;ZHOU Xuan;GUO Lu-qin;LI Na;ZHANG Yang;ZHAO Yan(Heilongjiang University of Chinese Medicine,Harbin 150040,China;The First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学,哈尔滨150040 [2]黑龙江中医药大学附属第一医院,哈尔滨150040

出　　处：《中华中医药杂志》2021年第8期4658-4663,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81973894);黑龙江中医药大学校研究生创新科研项目(No.2020yjscx003);黑龙江中医药大学科研基金项目(No.201826);中国博士后科学基金项目(No.2019M661320)。

摘　　要：目的:探究补肾活血方及有效组分药物血清对抗心磷脂抗体(ACA)阳性复发性流产(RSA)患者蜕膜基质细胞(DSCs)中TLR4/NF-κB通路的影响。方法:健康Wistar大鼠灌胃制备补肾活血方含药血清,使用高效液相色谱仪对含药血清及有效药物组分隐丹参酮进行测定。收集肾虚血瘀型ACA(+)RSA早期难免流产患者(病例组)和正常早期妊娠女性(对照组)的蜕膜组织,通过细胞培养技术建立人体外蜕膜细胞体系并完成DSCs鉴定。对照组和病例组DSCs按培养孔各随机分为9组。而后用荧光定量RT-PCR法检测各组别TLR4、NF-κB和COX-2 mRNA的表达量,印证补肾活血方及药物有效成分隐丹参酮对TLR4/NF-κB信号通路的调控作用。结果:与对照组比较,在ACA(+)RSA蜕膜细胞中TLR4、NF-κB和COX-2 mRNA表达量显著增加,补肾活血方含药血清及其有效组分能够有效抑制TLR4/NF-κB/COX-2信号通路的激活,促进COX2的表达。结论:补肾活血方及其有效药物隐丹参酮基于TLR4/NF-κB/COX-2信号通路调节蜕膜细胞功能,从而对肾虚血瘀型ACA(+)RSA发挥治疗作用。Objective:To investigate the TLR4/NF-κB pathway in decidual stromal cells(DSCs)of patients with ACA(+)recurrent spontaneous abortion(RSA)by Bushen Huoxu Decoction(BHD)and its active component serum.Methods:Healthy Wistar rats were given gavage to prepare the drug serum containing BHD,and the drug serum containing cryptotanshinone and the effective drug component were measured by HPLC.Decidual tissues of ACA(+)RSA patients(case group)and normal early pregnancy women(control group)were collected,and DSCs were cultured in vitro and DSCs identification was completed.DSCs in case and control groups were respectively divided into nine groups.The expression levels of TLR4,NF-κB and COX-2 mRNA in each group were detected by fluorescence quantitative RT-PCR to confirm the regulatory effects of BSD and cryptotanshinone on TLR4/NF-κB signaling pathway.Results:Compared with the control group,TLR4,NF-κB and COX-2 mRNA expression levels were significantly increased in DSCs of ACA(+)RSA.The serum containing BSD and its active components effectively inhibited the activation of TLR4/NF-κB/COX-2 signaling pathway and promoted the expression of COX2.Conclusion:BSD and its effective drug Cryptotanshenone regulate the function of DSCs based on TLR4/NF-κB/COX-2 signaling pathway,thus playing a therapeutic role on ACA(+)RSA patients with the type of kidney deficiency and blood stasis.

关 键 词：抗心磷脂抗体 复发性流产 TLR4/NF-κB/COX-2信号通路 补肾活血方 隐丹参酮 

分 类 号：R285.5[医药卫生—中药学]