基于黏附斑激酶跨膜信号系统探讨化瘀消癥复方对输卵管妊娠滋养细胞迁移的调控机制  

Regulatory mechanism of Huayu Xiaozheng Compound on the migration ability of tubal gestational trophoblastic cells based on the extracellular matrix-integrincytoskeleton transmembrane signaling system

作　　者：袁烁[1] 陈思达 陈敏红 邓高丕[1] YUAN Shuo;CHEN Si-da;CHEN Min-hong;DENG Gao-pi(Gynaecology Department,The First Affiliated Hospital of Guangzh ou University of Chinese Medicine,National Regional Chinese Medicine Gynecological Diagnosis and Treatment Center of South China,Guangzhou 510405,China;Gynaecology Department,Guangdong Provincial Hospital of Chinese Medicine,Guangzhou 51120,China)

机构地区：[1]广州中医药大学第一附属医院妇科,国家华南区中医妇科区域诊疗中心,广州510405 [2]广东省中医院妇科,广州51120

出　　处：《中华中医药杂志》2022年第6期3141-3146,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81804134);广东省自然科学基金项目(No.2018A030313469);邓高丕广东省名中医传承工作室(No.粤中医办函﹝2019﹞5号)。

摘　　要：目的:基于黏附斑激酶(FAK)为中心的细胞外基质-整合素-细胞骨架跨膜信号系统,探讨化瘀消癥复方对输卵管妊娠滋养细胞迁移的调控机制。方法:对输卵管妊娠绒毛滋养层细胞进行体外培养与鉴定,以含化瘀消癥复方水提液的培养基对输卵管妊娠滋养细胞进行培养,分为A(空白)组、B(FAK抑制剂Y15)组、C(Y15+中药中剂量)组、D(中药低剂量)组、E(中药中剂量)组、F(中药高剂量)组;应用Transwell法检测各组药物对滋养细胞迁移力的影响,Western Blot法检测各组药物对FAK、p-FAK、整合素β1(Integrinβ1)、桩蛋白(Paxillin)、尿激酶型纤溶酶激活物(uPA)蛋白表达的影响。结果:与A组比较,各给药组均能显著抑制细胞的迁移能力(P<0.05),各中药组呈一定的剂量依赖性;与A组、B组比较,C组、F组均可下调FAK、p-FAK、Integrinβ1、Paxillin、uPA蛋白表达水平(P<0.05);各中药组对蛋白的影响呈一定的浓度依赖性。结论:化瘀消癥复方可能发挥与FAK抑制剂类似的效应,起到抑制输卵管妊娠滋养细胞迁移的作用,其机制可能是与下调Integrinβ1,抑制FAK的信号转导,引起下游Paxillin的表达减少,负调控uPA,进而降调滋养细胞黏附斑激酶跨膜信号系统活性相关。Objective:To explore the regulatory mechanism of Huayu Xiaozheng Compound on cell migration of the tubal gestational trophoblast,through extracellular matrix-integrin-cytoskeleton transmembrane signaling system.Methods:The tubal gestational trophoblast cultured and identified in vitro were taken for study model.The cells were divided into 6 groups:group A(control),group B(FAK inhibitor Y15),group C(Y15 joined medium dose of Chinese medcine),group D(low dose of Chinese medcine),group E(medium dose of Chinese medcine),group F(high dose of Chinese medcine).The cell migration were detected by Transwell assay,while the protein expressions of FAK,p-FAK,Integrinβ1,Paxillin,uPA were detected by Western Blot.Results:Compared with group A,the cell migration was down-regulated in all giving drug groups(P<0.05)and it was positively correlated with the concentration of traditional Chinese medicine.Compared with group group A and group B,the expression levels of FAK,p-FAK,Integrinβ1,Paxillin and uPA protein were down regulated in group C and group F(P<0.05).The effect of each dose group of Chinese medicine on the protein was dose-dependent.Conclusion:Huayu Xiaozheng Compound may play a similar or synergistic effect with FAK inhibitors,inhibit the migration of tubal trophoblastic gestational cells,the mechanism may be via down-regulation of uPA expression associated with degradation of extracellular matrix.At the same time,the expression of FAK,p-FAK,and Paxillin are adjusted to inhibit the transmembrane signal transduction system of trophoblast.

关 键 词：化瘀消癥复方 输卵管妊娠 细胞迁移 黏附斑激酶跨膜信号系统 机制 滋养细胞 整合素Β1 桩蛋白 尿激酶型纤溶酶激活物 

分 类 号：R285[医药卫生—中药学]