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雌激素受体β基因在生理中的作用和机制
发布时间:2020-01-04

  摘    要: 雌激素受体β(estrogen receptor β, ERβ)是经典的核受体,属于核受体超家族成员。在体内起着重要的生物学作用,参与众多生理和病理活动,是多种癌症、心血管疾病、肥胖症、哮喘等药物的开发靶点,其特殊的药理活性可为众多的疾病带来更佳的治疗方案。现从ERβ的基因结构特征,生理、病理作用,作用机制及其未来的研究展望进行综述。

  关键词:赢发彩票代理 雌激素受体β; 结构特征; 作用机制; 生理作用; 病理作用;

  Abstract:赢发彩票代理 Estrogen receptor β(ERβ) is a classical nuclear receptor and belongs to the nuclear receptor superfamily. It participates in a variety of physiological and pathological activities in the body. It is an important target for a variety of cancers, cardiovascular diseases, obesity and asthma. Its unique pharmacological function provides better treatment options for many diseases. The genetic structure, mechanism of action, physiological effects, pathological effects and future research prospects of ERβ will be summarized in this review.

  Keyword: estrogen receptor β; structural characteristics; mechanism of action; physiological action; pathological effect;

  CIJISU(estrogen)SHIDUOZHONGBAZUZHISHENGZHANGHEFENHUADEGUANJIANDIAOJIEYINZI,JUYOUGUANGFANERZHONGYAODESHENGLIZUOYONG,QIBUJINCUJINCIXINGDONGWUDIERXINGZHENGFAYUJIXINGQIGUANDECHENGSHU,HAIJUYOUKANGYANGHUA、KANGYANZHENG、YIZHIZHONGLIUSHENGZHANGHEBAOHUXINXUEGUANXITONGDENGZUOYONG。CIJISUTONGGUOYUCIJISUSHOUTI(estrogen receptor,ER)TEYIXINGJIEHEERQIZUOYONG,CIJISUSHOUTISHIPEITIYILAIDEZHUANLUDIAOJIEYINZI,SHUYUHESHOUTICHAOJIAZUCHENGYUAN[1]。JINNIANLAIYANJIUFAXIANCIJISUSHOUTICUNZAIYUXIBAOMO、XIBAOZHI、XIBAOHEZHONG,KEFENWEILIANGDALEI:YILEISHIJINGDIANDEHESHOUTI,WEIYUXIBAOHENEI,TONGGUODIAOJIETEYIXINGBAJIYINDEZHUANLUERFAHUI“JIYINXING”DIAOJIEXIAOYING,ZHUYAOBAOKUOERαHEERβ;DIERLEISHIMOXINGSHOUTI,TONGGUODIERXINSHIJIANJIEDIFAHUIZHUANLUDIAOKONGZUOYONG,ZHUYAOBAOKUOJINGDIANDEHESHOUTIMOXINGCHENGFENYIJISHUYUGDANBAIOULIANSHOUTIJIAZUDEGPER1(GPR30)、Gαq-ERHEER-X。QIZHONGERβJIAOWEITESHU,TAJICUNZAIYUXIBAOHENEI,YECUNZAIYUXIBAOMO、XIANLITIZHONG。20SHIJI60NIANDAICHU,Elwood JensenJIQITONGSHISHOUCIBAODAOLECIJISUJIEHESHOUTIDANBAIDECUNZAI,GAISHOUTIDANBAIDEcDNAYEZAI20SHIJI80NIANDAIZHONGQIBEIKEXUEJIAKELONGCHULAI,BINGBEIMINGMINGCHENGERα[2]。ERαZAIHENZHANGDEYIDUANSHIJIANLIBEIRENWEISHICIJISUWEIYICUNZAIDESHOUTI,YINCI,DANGSHIYOUHENDUODESHENGLIXIANXIANGWUFAJIESHI。1996NIAN,KuiperDENG[3]CONGDASHUDEQIANLIEXIANZHONGKELONGCHULINGYIZHONGXINDECIJISUSHOUTI,MINGMINGWEIERβ。YUERαDEGUANGFANFENBUBUTONG,ERβJINZAILUANCHAO、SHENZANGZUZHI、NAOZUZHI、JIECHANGDENGZHONGBIAODAJIAOGAOSHUIPINGDEm RNA[4]。ERαYUERβZAIJIEGOUSHANGYOUGAODUDETONGYUANXING,DANZAIBIANMAJIYIN、ZUZHIFENBUHEZAIGEZUZHIZHONGDEBIAODAMINGXIANBUTONG,YOUQISHIYUPEITIJIEHEHOUCHANSHENGDESHENGLIXUEXIAOYINGYEBUTONG[5]。XIANGBIYUERα,ERβZAIZHILIAOAIZHENG、XINXUEGUANJIBING、XIAOCHUANDENGYINGYONGZHONGJUYOUGENGZHONGYAODEZUOYONG。BENWENJIANGJIANGSHUERβDEJIYINJIEGOUTEZHENG,ERβJIYINZAISHENGLIZHONGDEZUOYONGHEJIZHIYIJIWEILAIDEYANJIUFANGXIANG。

  1、 ERβ的基因结构特征

  人的ERβ基因位于染色体14q23.2,有8个外显子,编码成一个由530个氨基酸组成的蛋白质[6]。ERβ是核受体超家族的成员,与该家族的其他成员结构相似,含有五个可区分的区域,分别被命名为A/B、C、D、E/F域,其结构域如图1所示[7]。处于N末端的是A/B结构域,是最易变的区域。人的ERα和ERβ在该区域的氨基酸同源性小于20%,表明该结构域可能对靶基因的ER亚型有特异性作用。在A/B区域中有一个转录激活功能区1(activation function 1,AF1)和NH2末端域(NH2-terminal domain,NTD),它是非配体依赖性的,通过与基础转录因子、辅助激活因子以及其他转录因子的相互作用,起到启动和激活靶基因的作用。中心C区域是一个DNA结合区(DNA binding domain,DBD),其参与DNA的特异性结合和受体二聚化。该区域是一个富含碱性氨基酸和半胱氨酸的高度保守区,95%的氨基酸具有同源性。D结构域是多变铰链区(hinge region),在DBD与配体结合区域(ligand binding domain,LBD)之间起柔性铰链的作用,其可使受体弯曲、翻转或者改变构象从而形成受体二聚体。D区中还包括具有稳定DNA结合作用的核定位信号(nuclear localization signal,NLS)。Ε结构域即配体结合区域LBD,ERα和ERβ基因的氨基酸在该区域具有55%的一致性。LBD中含有激素依赖的激活功能区2(activation function 2,AF2),其对配体结合和受体二聚化具有重要意义。ERα和ERβ的配体结合区域具有非常相似的三维结构,但配体结合腔内的氨基酸在两个位置上不同,且ERβ的配体结合腔比ERα小约20%,这可能是导致不同配体选择性、亲和力以及药理学作用的原因。F区是由42个氨基酸残基组成的,其是激活转录以及发挥雌激素药物作用的必需组分[4]。
 

雌激素受体β基因在生理中的作用和机制
 

  2、 ERβ的生理应用及作用机制

赢发彩票代理   ZAIGUOQUDEJINIANZHONG,ERβYIBEIZHENGMINGZAITINEICUNZAIYULUANCHAO、SHENZANG、NAO、JIECHANGDENGZUZHIZHONGBINGCANYUDUOZHONGSHENGLIHEBINGLIHUODONG。XIANQIANRENMENDEYANJIUGENGDUODIJUJIAOYUERβYUQIANLIEXIANAI、RUXIANAI、JIECHANGAIYIJIXINNAOXUEGUANJIBINGDENGDEGUANXI,JINQIXIANGGUANDEYANJIUBIAOMING,LIYONGERβJIYINYENENGJIJIJIANBING、XIAOCHUANZHENG、FEIPANGZHENGDENGJIBINGDAILAIXIWANG。ERβDESHENGLIZUOYONGWANGWANGSHEJIDUOGEBADIAN,YUHENDUOJIBINGDEBINGYIN、FABINGJIZHIJIGEXITONGJIANDEXIANGHUGUANXISHIFENFUZA,BENWENXUANQULEQIDUIYINGDEJIZHILAIJINXINGCHANSHU。

  2.1、 癌症

赢发彩票代理   RUXIANAI(breast cancer)SHIFASHENGZAIRUXIANXIANSHANGPIZUZHIDEEXINGZHONGLIU,QIFABINGLVHUISUIZHENIANLINGZENGZHANGERZENGJIA,QIZHONG80%FASHENGZAI50SUIYISHANGDEFUNVZHONG[8]。YUE70%DERUXIANAIDOUSHICIJISUYILAIXINGDE,DANGQUEFAYILAIDEJISUSHIZHONGLIUHUIXIAOTUI[9]。ERαHEERβDUIRUXIANZUZHIYOUJIERANBUTONGDEYINGXIANG:ERαCUJINAIXIBAODESHENGZHANGHEZENGZHI,ERERβZEYIZHIZHONGLIUZENGZHIFENHUABINGCUJINDIAOWANG[10]。YINCI,LIYONGERβJIYINZHILIAORUXIANAISHIYIZHONGYOUXIAOZHILIAOFANGAN。SHIYONG20nmol/LDEERβJIDONGJIERFANGJIBINGJING(C15H13N2,DPN)CHULISANYINXINGRUXIANAI(triple negative breast cancer,TNBC)XIBAO,SHIYANJIEGUOXIANSHIZHONGLIUXIBAODEZENGZHIHEQIANYILVXIANZHEJIANSHAO,ERJIANGERβQIAOCHUZEKEDAOZHIZENGZHIXIANXIANGDEFASHENG[11]。SongDENG[12]JIANGERβZHUANRURUXIANAIXIBAODEXIANLITI,XINGCHENGXIANLITIERβ(mito ERβ),ZAIDONGWUMOXINGZHONGmito ERβDEGUOBIAODAYIZHILETNBCXIBAOHEZHONGLIUKUAIDEZENGZHI,QIJIHUOLEYANGHUALINSUANHUA(oxidative phosphorylation,OXPHOS)XITONGCONGERYIZHILETNBCXIBAODEZENGZHI。AnestisDENG[13]YANJIUFAXIANERβJIYINKEZENGJIATNBCZHONGXIONGJISUSHOUTI(androgen receptor,AR)DEYIZHIJIENZALUANDEMINGANXING,ERARQUEDUITNBCJUYOUCUJINZUOYONG,CONGERZENGQIANGKANGZHONGLIUZUOYONG;ERβKEJIANJIETONGGUOYIZHIPI3K/AKTXINHAOZHUANDAOTUJINGLAIJIANGDIARDEHUOHUA,YEKEZHIJIEZAIMDA-MB453XIBAOHUORENZUZHIYANGPINZHONGYUARXINGCHENGYIERJUTI,ZUZHIXINGCHENGTONGYUANERJUTI。

  图1 ERα和ERβ的结构域[7]
图1 ERα和ERβ的结构域[7]

  QIANLIEXIANAI(prostate cancer,PC)SHIFASHENGZAIQIANLIEXIANSHANGPIDEEXINGZHONGLIU,QIFABINGLVYUZHONGZU、DILIWEIZHI、XINGHUODONG、YINSHIXIGUANHEYICHUANYINSUDENGYOUGUAN[14]。ERβYINQIKEJIANSHAOAIXIBAOZENGZHIDETEXINGZHENGZAICHENGWEIHUAXUEYUFANGQIANLIEXIANAIDEQIANZAIMUBIAO。ColciagoDENG[15]CEDINGLERENQIANLIEXIANAIXIBAORv1MANXINGBAOLUYUERβXUANZEXINGPEITIDPN、3β-ADUOCHUN(QIANLIEXIANZHONGDENEIYUANXINGPEITI)DENGZHIHOUDEXIBAOZENGZHILV,FAXIAN3β-ADUOCHUNKEYITONGGUOERβYIZHIQIANLIEXIANAIDEKUOZENG。ERβHEXINZHIhomeobox 3(ZFHX3)KANGTILIANYONGKEDIAOJIEXIAOSHUQIANLIEXIANFAYUBINGYIZHIQIANLIEXIANZHONGLIUDEFASHENG,ZAILNCaPHEC4-2BDENGQIANLIEXIANAIXIBAOXIZHONG,ERβKEMINGXIANYIZHIZHONGLIUHUOXING[16]。YANJIUFAXIANSHUYUZAODAI(dioscin)KETONGGUOQIANGQINGJIANHESHUSHUIZUOYONGDUIERβCHANSHENGQIANGLIEDEQINHEZUOYONG,JIHUOERβJIYINCONGERFAHUIQIANGXIAODEKANGQIANLIEXIANAIHUOXING[17]。

赢发彩票代理   JIEZHICHANGAI(colorectal cancer,CRC)SUIRANKUOSANHUANMAN,KEYITONGGUOWULIJIANCHAZAOQIZHENDUANCHULAI,DANSHIMUQIANDEYUFANGGONGZUORENGBUWANSHAN。JIEZHICHANGAIJUYOUJIAOGAODESIWANGLV,JUEJINGQIANNVXINGHUANCRCDEFENGXIANYUANDIYUNANXING[18],NANXINGHUANCRCDEZONGFENGXIANBINVXINGGAO60%[19]。DANSHINVXINGJUEJINGHOUGAIFENGXIANXUNSUTISHENG,DUOZHONGZHENGJUBIAOMINGCIJISUSHIZHEIZHONGBAOHUZUOYONGDEJICHU。WilliamsDENG[20]FAXIANERβJIYINQUESHIYINGXIANGCRCCHANGAIMOXINGZHONGZHONGLIUDEXINGCHENG,BINGQIESHIYONGJIDONGJIERFANGJIBINGJING(DPN)HOUFENBIESHIDONGWUMOXINGZHONGXIONGXINGHECIXINGXIAOSHUDECHANGZHONGLIUFASHENGJIANSHAOLE39%HE36%。ERβDEQUESHIHUIJIAJUCRCZAOCHENGDECHANGDAOWEISHENGWUQUNDUOYANGXINGDEJIANSHAO,CONGERYINGXIANGMIANYIXITONGJIBINGHEDAIXIEGONGNENG。SHIYANBIAOMINGERβYOUZHUYUCHANGDAOWEISHENGWUZUSHENGZHANG,KEYIJIANSHAOCRCDEZENGZHI[21]。ZhaoDENG[22]FAXIANCONGZHONGCAOYAOHUANGQIZHONGTIQUDECHENGFENMAORUIHUASUTONGGUODIAOJIEERβJIEDAODEIGF-1R、PI3K/AktXINHAOZHUANDAOTUJINGHEmi R-95DEBIAODA,ZAITINEIHETIWAIDOUKEDUICRCXIBAODEZENGZHIFAHUIYIZHIZUOYONG。

  ERβJIQIJIDONGJIZAIZHILIAOAIZHENGSHI,QIJIZHISHIKEYITONGGUOJIHUOZHONGLIUXIBAOFENMIZHONGLIUHUAISIYINZIα(TNFα)LAIYIZHIZHONGLIUSHENGZHANG[23]。ZAICRCZHONGERβBEIRENWEISHIBAOHUYINZI,QITONGGUOSHANGDIAOMLH1JIYINDEBIAODA,BINGYUTINEIWAIDE5-FUNIAOMIDING(5-FU)JIEHE,DUICRCZHONGLIUDEZENGZHIQIYIZHIZUOYONG,HAIKETONGGUOp53XINHAODIAOJIEDNAXIUFU,TONGGUODIAOJIEG1QIXIBAOZHOUQIJIYINLAIJIANSHAOJIECHANGAIXIBAODEXIBAOZENGZHI[24]。ERβTONGGUOYIZHIPI3K、p45Skp2、c-mycHEcyclin EDENGGUANJIANZHIAIJIYIN,TIGAOXIBAOKANGZHONGLIUHUOXING,BINGTIGAOKANGZENGZHIJIYINRUPTEN、FOXO3、KLF5、p21WAF1、CDKN1AHEp27Kip1DEBIAODALAIJIANHUANZHONGLIUXIBAODEZENGZHI[25]。

  2.2、 心血管疾病

赢发彩票代理   GENJUSHIJIEWEISHENGZUZHIDETONGJISHUJU,NANXINGDEXINNAOXUEGUANJIBINGFASHENGLVYUANGAOYUJUEJINGQIANDENVXING,DANSHINVXINGDEZHEIZHONGYOUSHIHUISUIZHENIANLINGDEZENGZHANGERXIAJIANG,BINGQIEZAIJUEJINGHOUFABINGLVHUIJIJUSHANGSHENG。YANJIUZHENGMINGXINNAOXUEGUANDEJIBINGYUTINEIDECIJISUSHUIPINGYOUGUAN,ZHEIYESHUOMINGERβKEZUOWEIXINXUEGUANXITONGDEBAOHUJI。

  XINJIFEIHOU(cardiac hypertrophy)SHIZHIXINZANGWEISHIYINGDUOZHONGCIJIERZAOCHENGDEXINJIXIBAOTIJI、ZHONGLIANGZENGJIA,QIHUIZAOCHENGBAOKUOXINJIXIBAOFEIDA、XINJIJIANZHIXIBAOZENGZHIYIJIXINZANGXIBAOWAIJIZHIGAIJIANDENGDUOFANGMIANDEGAIBIAN[26]。TsaiDENG[27]ZAIH9C2XINJIXIBAOHEXINSHENGDASHUXINSHIJIXIBAO(NRVM)ZHONGJIANLILEERβJIYINBIAODAXITONG,GAIYANJIUTONGGUODANBAIZHIYINJI、JIDONGDANBAIRANSEHEHUOHUATXIBAOHEYINZI(nuclear factor of activated T cells,NFAT)YIWEIDENGFAXIANYIBINGSHENSHANGXIANSUTONGGUOGAIDIAOSHENJINGLINSUANMEIYOUDAOXINZANGFEIDA,ERERβKETONGGUOJIANGDIYIBINGSHENSHANGXIANSUERYIZHIXINJIXIBAOFEIDA。ZAIRENTIZHONG,XUEGUANJINZHANGSUII(AngII)JIANJIEHEZHIJIEDICIJIXINZANGFEIDA,AngIICIJIZHUANHUASHENGZHANGYINZIβZAIJIXIBAOBIAODA,TONGGUOTAK1JIMEIJIHUOP38αMEI,YIZHIKLF15BIAODA,ERKLF15DEZHUANLUYINZIJUYOUKANGFEIDAZUOYONG,CIJISUTONGGUOERβQIZUOYONGYIZHIAngIIDEHUOXING[28]。GUOBIAODADEERβYIZHILELIANGANSUANLALIANHEWUJUNαJIXUJIMEI(leucine zipper-and sterileαmotif-containing kinase,ZAK)BINGYOUXIAODIYIZHILEp-JNK、p-p38、c-JunHEGATA-4DENGDESHUIPING,QIHAIYIZHIE3 ligase-casitas B-lineage lymphoma(CBL)DEFENMIBINGQIEJIANSHAOQIHECBL-phosphoinositide 3-kinase(PI3K)DEJIEHE,YIFANGZHIPI3KJIANGJIE,CONGERYIZHIYOUZAKYOUDAODEXINJIFEIDAHESUNSHANG[29]。

  XINLISHUAIJIE(heart failure,HF)SHIXINJIZHONGSUDEJINXINGXINGJIBING,QITEZHENGSHIXINLISHUAIJIEHUANZHEXINZANGSHOUSUN,DAOZHISHOUSUOHESHUZHANGGONGNENGYIJIXUNHUANCHONGXUEGONGNENGJIANRUO[30]。IorgaDENG[31]FAXIANSHIYONGCIJISUKEYITONGGUOJIHUOERβWANJIUXINLISHUAIJIE。SHIYANZHONGTONGGUOHENGXIANGSUOZHAIXIONGXINGDASHUDEZHUDONGMAIYOUDAOYANZHONGDEHF,DANGSHEXUEFENSHU(EF)DADAOYUE35%SHI,SHIYONGERβDEJIDONGJICHIXUZHILIAO10 d,JIEGUOBIAOMINGCIERCHUN(E2)TONGGUOERβJUYOUZHILIAOYANZHONGHFDEGONGXIAO。PelzerDENG[32]FAXIAN,ERβJIYINQUESHIDECIXINGXIAOSHUYUYESHENGXINGXIANGBIHUIJIAZHONGXINLISHUAIJIEZHENGZHUANG,BINGDAOZHIXINJIGENGSICONGERSIWANGLVSHENGGAO。

赢发彩票代理   ZAIBAOHUXINXUEGUANFANGMIAN,ERβDEZUOYONGJIZHISHIQIKEZENGJIAXIBAONEIDENotch1DESHUIPING,ERNotch1DEGUOBIAODAKEYIXIANZHEJIANSHAONEIPIXIBAOZHONGDETNFαDECUDIAOWANGXIAOYING[33]。QIBAOHUBUFENHAIGUIGONGYUTONGGUOJIHUOXUEGUANNEIPISHENGZHANGYINZI、JIANXINGCHENGXIANWEIXIBAOSHENGZHANGYINZIHEHUANYANGHEMEI2LAICIJIXUEGUANSHENGCHENG,YIZHIXUEGUANXIANWEIHUA,HUIFUXUEYEDONGLIXUECANSHU。GUOBIAODADEERβYOUXIAODIYIZHILEZAK、p-JNK、p-p38、c-JunHEGATA-4DENGDESHUIPING,CONGERBAOHUXINJIBIMIANSUNSHANG[34]。

  2.3、 其他疾病

  JIJIANBINGSHIYOUZHONGFUDESHOUSHIHEYUNDONGYINQIDEJIROUGUGEJIBING,BEIRENWEISHIJIROUGUODUSHIYONG,FANFUQIANGLIEQIANLAYINQIDEZONGHEZHENG。HsiehDENG[35]FAXIANLIYONGCIJISUHEERβKEYIDIAOJIEZHILIAOBINGBIANDEJIJIAN。TAMENGOUJIANLEDASHUJIJIANBINGMOXING,FENLIPEIYANGYUANDAIJIJIANXIBAO,JINXINGMIANYIYINGGUANGHETUNELPINGGU。JIEGUOFAXIAN,ZAIJINGLIJIXIEFUHEHECIJISUQUEFAXIADEJIJIANXIBAOTONGGUOSHANGDIAOERβDESHUIPINGHEYOUDAOXIBAODIAOWANGERJIAJUJIBING。DONGWUSHIYANZHONGZHANGQIJIYAODPNKEYIHUIFU10ZHONGYINLUANCHAOQIECHUSHUERYINQIDEGUHEGUSUIZHONGm RNADEYICHANGBIAODA[36]。ERβXIANGGUANDEXIBAODIAOWANGDUIJIJIANBINGBIANDEFABINGJIZHIZHIGUANZHONGYAO,ZHEIXIEFAXIANKENENGYOUZHUYUKAIFAZHENDUIJIJIANXIANGGUANJIBINGZHONGBAXIANGERβXINHAOZHUANDAOTUJINGDEXINXINGYAOLIXUELIAOFA。

  FEIPANGZHENGZHUYAOSHIYINWEIRELIANGSHERUDUOYUXIAOHAOHUOZHIFANGDAIXIEWENLUANERDAOZHIDUOYURELIANGYIZHIFANGXINGSHICHUCUNYUTINEIERZAOCHENGFEIPANG。FEIPANGZENGJIALEHUANGAOXUEYA、TANGNIAOBING、ZHIFANGGAN、GUGUANJIEJIBING,SHENZHIAIZHENGDENGDEFENGXIAN,QIYUSIWANGLVYECHENGZHENGXIANXINGGUANXI。MUQIANLINCHUANGSHANGQUEFAKEKAODEKANGFEIPANGYAOWU,DADUOSHUYAOWUYIKAOYINYOUHUANZHEDEBAOFUGANLAIJIANGDITIZHONG,ZHEIZHONGFANGFAWUFAZHANGSHIJIANBAOCHITIZHONGJIANSHAO,BINGQIECUNZAIXUDUOFUZUOYONG。JINGYANZHENG,TONGGUOERβJIYINZHILIAOFEIPANGZHENGSHIYIZHONGKEXINGDEFANGFA。DONGWUSHIYANFAXIANQIECHULUANCHAO8ZHOUHOU,OVXDASHUTIZHONGMINGXIANZENGJIA,TONGSHINEIZANGZHIFANGCHENJI,ZAOCHENGDASHUFEIPANG[37]。González-GranilloDENG[38]DUIWEIQIECHULUANCHAODECIXINGXIAOSHUJINXINGGAOZHIFANGWEISHI,TONGSHISHIYONGERβXUANZEXINGPEITI4-[2-(3,5-ERJIAJIYIEZUO-4-JI)-1H-YINDUO-3-JI]BENFEN(DIP)JINXINGSHENGLIGANYU,BINGDUIXIAOSHUTINEIERβSHOUTIBADIANXUANZEXINGJIHUO。JIANCEFAXIANDIPKETONGGUOJIANSHAOCIXINGXIAOSHUGANZANG、PIXIAZHIFANGZUZHI(SAT)HENEIZANGZHIFANGZUZHI(VAT)DEZHIZHICHUCUNERXIANZHEJIANGDIXIAOSHUTIZHONG,BINGWUXUDIAOZHENGXIAOSHUSHILIANGHEHUODONGLIANG[39]。ERβJIYINZHILIAOFEIPANGZHENGDEZUOYONGJIZHISHIERβJIQIXUANZEXINGPEITIKEYIJIANGQIANZHIFANGXIBAOHEQIANTIGANXIBAOZHONGXINBIANMAZHUANHUACHENGWEIZONGSEZHIFANGZUZHI,BINGQIEKEYIZENGJIAXIANLITIHUODONG,ERZENGJIAZONGSEZHIFANGZUZHISHIZHILIAOFEIPANGZHENGDEZUIJIAZHILIAOFANGFA,QINENGXIAOHAODALIANGDENENGLIANG,CONGERJIANQINGTIZHONG[39]。

赢发彩票代理   XIAOCHUANSHIYIZHONGCHANGJIANDEMANXINGQIDAOYANZHENG,SHEJIDUOZHONGXIBAOJIXIBAOZUFEN。YANZHENGDAOZHIFEIBUNIANYEJIJU,QIDAOJINYIBUSUOXIAO,YINQIHUXIKUNNANHEQITABINGFAZHENGDEFAZUO[40],XIAOCHUANDEBIAOZHIXINGTEZHENGSHICHIXUXINGYANZHENGCUJINQIDAOPINGHUAJI(ASM)XIBAOZENGSHENG。AmbhoreDENG[41]SHIYONGXUEXIAOBANYANSHENGSHENGZHANGYINZI(PDGF)、17β-CIERCHUN、ERαHEERβ、GPR30DEJIDONGJIFENBIECIJIYUANDAIRENASMXIBAO,BINGSHIYONGMTTFACEDINGZENGZHIBIANHUA。SHIYANJIEGUOXIANSHI,PDGFXIANZHECUJINLEXIAOCHUANXIBAOASMDEZENGZHI,ERERβDEJIHUOKEYIYIZHIPDGFYOUDAODEMAPKHEPI3KXINHAOTONGLUZENGZHI,CONGERYIZHIXIAOCHUANXIBAOASMZENGZHI,QIDAOZHILIAOXIAOCHUANDEZUOYONG。SHIYONG10 nmol/LCIJISUCIJIQIGUANMOXING,JIEGUOXIANSHIKEYISHIRENQIDAOPINGHUAJISONGCHI,YOUDAOZHIQIGUANKUOZHANG,BIAOMINGCIJISUDUIQIDAOSHOUSUOJUYOUBAOHUZUOYONG[42]。ZHILIAOXIAOCHUANDEZUOYONGJIZHISHIERβDUIYANZHENGGUOCHENGZHONGDEP2X3SHOUTIJUYOUYIZHIZUOYONG,ERP2X3SHOUTIDEJIHUOZECUJINYANZHENGDEFASHENG。CIWAILIYONGERβJIYINHAIKEYIZHIP2X3SHOUTIZAICHUJIGANJUESHENJINGYUANZHONGDEBIAODAHEGONGNENG,JIANQINGYANZHENGZHONGDETENGTONGGANZHI[43]。

  3、 结语与展望

赢发彩票代理   ZAITINEIERβJIYINJINENGSHANGDIAOMLH1、Notch1DENGDESHUIPING,YENENGYIZHIP2X3SHOUTI、MAPKHEPI3KXINHAOTONGLU,YINQITESHUDESHENGLIZUOYONGERBEIYUNYONGYUXINXUEGUANJIBING、AIZHENG、JIJIANDENGJIBINGDEZHILIAO。YINCI,XUYAOJINYIBUKAIZHANERβZUOYONGDEFENZIJIZHIYANJIU,KAIFACHUGENGDUOYIERβWEIBADIANDEXUANZEXINGSHOUTIDIAOJIEJI(SERM),SHIERβZAIZHENGCHANGSHENGLIHEBINGLIZHILIAOGUOCHENGZHONGFAHUIGENGDADEZUOYONG。DANSHI,CIJISULIAOFAYESHIYIBASHUANGRENJIAN,YUNYONGDEDANGCAINENGZHIYUJIBING。LIRUERβBINGBUSHIDUISUOYOUDEAIZHENGDOUYOUXIAODE,DUIYUBANGGUANGAI(BCa)ERβJIYINZEHUITONGGUOGAIBIANmiR-92aJIEDAODEDAB2IPXINHAOLAIZENGJIABCaXIBAODEZENGZHIHEQINXI[44]。SHIYONGQIANHAIXUYAOQUEDINGERβJISULIAOFAZHONGDEZUIDIQIXIAOLIANG,YINWEIJISUDESHIYONGWANGWANGSHIYIGEXINHAOFANGDADEGUOCHENG,RUGUOCHAOCHUYIDINGDESHIYONGJILIANGFANERHUIDAOZHIYOUFAAIZHENGDEFENGXIANDAFUZENGJIA。SUOYI,XUJIANGERβDEZUOYONGJIZHIYUJIBINGDEFABINGJIZHIRONGHUIGUANTONG,BINGQIEDUIZHENGXIAYAOCAINENGFAHUICIJISULIAOFADEGONGXIAO。

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