王大维,汪梅姣,谷焕鹏,温成平

• 1:浙江中医药大学基础医学院

摘要(Abstract)：

目的观察解毒祛瘀滋阴药含药血清对雌激素受体α和β及其相关通路的调节作用,从而探讨解毒祛瘀滋阴药治疗系统性红斑狼疮(SLE)的机制。方法 CCK-8法检测研究解毒祛瘀滋阴药含药血清对MCF-7细胞增殖的影响;以FITC-Annexin V/PI双染法流式细胞术检测10%解毒祛瘀滋阴药含药血清诱导MCF-7细胞的凋亡率;Realtime-PCR法检测ERα和PI3KmRNA的表达;Western blot法检测雌激素受体相关信号通路蛋白ERα、p-ERα、ERβ、ERK、p-ERK的表达。结果 10%和15%的解毒祛瘀滋阴药含药血清与空白血清相比均能较轻的抑制MCF-7细胞的增殖(P<0.01)。与空白血清相比,10%的解毒祛瘀滋阴药含药血清:使MCF-7细胞的早期凋亡较多;使ERα和PI3K的mRNA相对表达量明显降低(P<0.05或P<0.01);使ERα的蛋白表达和磷酸化水平降低;使ERβ的蛋白表达水平升高;使ERK的蛋白表达和磷酸化水平降低。结论下调ERα的表达和其磷酸化水平,促进ERβ的表达,下调ERK及其磷酸化进而影响MAPK/ERK信号通路也许是解毒祛瘀滋阴药治疗SLE的部分机制。

关键词(KeyWords)： 解毒祛瘀滋阴药;雌激素受体;信号通路;系统性红斑狼疮

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81373633);; 浙江中医药大学校级科研基金项目(2012ZY01)

作者(Author): 王大维,汪梅姣,谷焕鹏,温成平

参考文献(References)：

• [1]Tedeschi SK,Bermas B,Costenbader KH.Sexual disparities in the incidence and course of SLE and RA[J].Clinical Immunology,2013,149(2):211-218.
• [2]Cohensolal JFG,Jeganathan V,Grimaldi CM,et al.Sex hormones and SLE:influencing the fate of au toreactive B cells[J].Current Topics in Microbiology&Immunology,2006,305(305):67-88.
• [3]Incorvaia E,Sicouri L,Petersenmahrt SK,et al.Hormones and AID:balancing immunity and autoimmunity[J].Autoimmunity,2013,46(2):128-137.
• [4]Phadungkiatwattana P,Sirivatanapa P,Tongsong T.Outcomes of pregnancies complicated by systemic lu pus erythematosus(SLE)[J].Journal of the Medical Association of Thailand=Chotmaihet thangphaet,2007,90(10):1981-1985.
• [5]温成平,范永升,唐晓颇,等.解毒祛瘀滋阴药对系统性红斑狼疮患者性激素水平的调节作用[J].中国中西医结合肾病杂志,2003,4(10):580-582.
• [6]Rojasvillarraga A,Torresgonzalez JV,Ruizsternberg M.Safety of hormonal replacement therapy and oral contraceptives in systemic lupus erythematosus:a systematic review and metaanalysis[J].Plos One,2017,9(8):e104303.
• [7]Patrone C,Cassel TN,Pettersson K,et al.Regulation of postnatal lung development and homeostasis by estrogen receptorβ[J].Molecular&Cellular Biology,2003,23(23):8542-8552.
• [8]Zhang D,Trudeau VL.Integration of membrane and nuclear estrogen receptor signaling[J].Comparative Biochemistry&Physiology Part A Molecular&Integrative Physiology,2006,144(3):306-315.
• [9]Acconcia F,Kumar R.Signaling regulation of genomic and nongenomic functions of estrogen receptors[J].Cancer Letters,2006,238(1):1-14.
• [10]Ascenzi P,Bocedi A,Marino M.Structure-function relationship of estrogen receptor alpha and beta:impact on human health[J].Molecular Aspects of Medicine,2006,27(4):299.
• [11]Harris HA.The unexpected science of estrogen receptor-beta selective agonists:a new class of anti-inflammatory agents[J].Nucl Recept Signal,2005(4):e012.
• [12]Cheng L,Li J,Han Y,et al.PES1 promotes breast cancer by differentially regulating ERαand ERβ[J].Journal of Clinical Investigation,2012,122(8):2857.
• [13]BynotéKK,Hackenberg JM,Korach KS,et al.Estrogen receptor-alpha deficiency attenuates autoimmune disease in(NZB x NZW)F1 mice[J].Genes&Immunity,2008,9(2):137.
• [14]Thomas C,Rajapaksa G,Nikolos F,et al.ERβ1 represses basal-like breast cancer epithelial to mesenchymal transition by destabilizing EGFR[J].Breast Cancer Research,2012,14(6):R148.
• [15]范宇,付丽.雌激素受体与乳腺癌[J].诊断病理学杂志,2007,14(2):81-85.
• [16]Creighton CJ,Fu X,Hennessy BT,et al.Proteomic and transcriptomic profiling reveals a link between the PI3K pathway and lower estrogen-receptor(ER)levels and activity in ER+breast cancer[J].Breast Cancer Research,2010,12(3):R40.