亚投彩票

高胆固醇饲料建立小鼠胆结石模型的研究

译者导读:这是一篇关于构建小鼠胆结石疾病模型以研究人类胆结石形成机制的文章,该文论述了小鼠胆结石模型建立的研究历程,指出了人类胆结石形成机制的新思路。

重点是,文章总结了诸多研究的过程与结果,这些研究通过结合基因组学方法和小鼠表型研究成功鉴定了Lith基因,为人类Lith基因的发现推平道路。用基因敲除或转基因方法为胆结石这种“古老而又新鲜”的肝胆疾病的病理生理学研究提供了新的视角。对于从事胆结石课题研究、动物模型建立、高胆固醇饲料制备等工作的研究者来说,此文值得一读。

作者:Tony Y. Wang、Piero Portincasa等

译者:协同生物苏永腾博士

前言

DANJIESHISHIZUICHANGJIANDEGANDANJIBINGZHIYI,12%MEIGUOCHENGNIANRENSHENSHOUQIHAI,WEIJIANSHAODANJIESHIDEFABINGLV、SIWANGLV,SHENRUYANJIUDANJIESHIDEBINGLISHENGLIXUEJIANGYOUZHUYUKAIFACHUCHUANGXINYOUXIAODEZHILIAOFANGFA。

CONG20SHIJI50NIANDAIKAISHI,YANJIUZHEJIUTONGGUOJICANGSHU、LAOSHU、TUNSHU、TUZIHEHOUZIDENGSHIYANDONGWUWEIYANGSHUZHOUDAOJIGEYUEDEGAODANGUCHUNSILIAOBINGCHENGGONGJIANLILEDANJIESHIMOXING,CONGERGENJUMOXINGYANJIUDANJIESHIJIBINGDEFABINGJIZHI。ZHIZHISHANGSHIJI90NIANDAI,DIYIGEYUDANJIESHIXIANGGUANDEJIYIN-Lith1ZAIJINJIAOXIC57L/JXIAOSHUZHONGDEYIJIANDING。

YATOUCAIPIAOTONGGUOCIWENJIESHAOXIAOSHUDANJIESHIMOXINGDEJIANLI、MOXINGDUIYICHUANYANJIUYIJIDANJIESHIBINGLISHENGLIXUEYANJIUDEGONGXIAN,WEIDANJIESHIYANJIUZUOYIGEGAILANZONGSHU。

小鼠胆结石模型的建立

TeppermanDENGYANJIUZHELVXIANFAXIANKEYITONGGUODANGUCHUNHEDANSUANDEZUHESHIYONGLAIJIANLIXIAOSHUDANJIESHIMOXING。ZAIWEIYANGHANYOUDANGUCHUNHEDANSUANDESILIAOHOU,FAXIANCONGXIAOSHUDANSHIZHONGTIQUCHULAIDEZAICHUNJIBENSHANGSHIDANGUCHUN,ZHANLEJIESHIZONGZHONGLIANGDE94%,ERDANDUWEIYANG1%DANGUCHUNSILIAO2-8GEYUEQUEBUNENGYOUFACHUDANJIESHI。YOUCIKEJIAN,DANSUANZAIXIAOSHUDANJIESHIMOXINGJIANLIZHONGBIBUKESHAO。

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GENGZHONGYAODESHI,WangDENGRENFAXIANXIAOSHUWEIYANGGAODANGUCHUNSILIAO8ZHOUNEIDANGUCHUNJIEJINGHEDANJIESHIXINGCHENGDEJUTIGUOCHENG,XIANSHIZHANDANBAININGJIAODECHUSHIJILEI,JIERCHUXIANWUSHUIHUOYEJINGZHUANGWAIGUAN,RANHOUZHEIXIEDANGUCHUNJINGTIJUJI,ZUIHOUCHUXIANSHAZHIJIESHIHEZHENDANJIESHI(JIANXIATU)。

胆结石易感小鼠C57L/J饲喂高胆固醇饲料8周内胆固醇结晶和胆结石形成的显微照片(用相衬法,偏光显微镜)

(a)粘蛋白凝胶;(b)小液晶;(c)聚集液晶;(d)具有麦芽交叉双折射和焦点圆锥结构的熔融液晶;(e)弧形(可能是无水胆固醇)晶体;(f)丝状晶体;(g)端部管状晶体破裂产生胆固醇一水合物晶体;(h)典型的胆固醇一水合物晶体,从28和100.88的角度;(i)聚集的胆固醇一水合物晶体;(j和k)砂质结石;(l)胆结石。

小鼠模型对胆结石遗传学研究的贡献

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SUIHOU,C57L/JHEAKR/JXIAOSHUDEGAN、DANNANG、XIAOCHANGDENGBUWEIDOUBEIYONGLAIJINXINGLEXITONGDEJIYINBIAOXINGDUIBIYANJIU。WEILEPANDUANLith1HELith2LIANGGEJIYINZHONGNAGEDANDUYOUDAODANJIESHIDECHANSHENG,XIEDAILith1DEC57L/JXIAOSHU(DANJIESHIYIGAN)HUOLith2DENGWEIJIYINDEAKR/JXIAOSHU(KANGDANJIESHI)MOXINGBEIJIANLIBINGJINXINGZHISHIYANJIU,JIEGUOFAXIANLith1HELith2TONGGUOBUTONGDECHENGSHIJIZHIYOUDAODANJIESHIDEFASHENG,Lith1DIAOKONGDANGUCHUNDEDAIXIE,Lith2ZEYUDANZHISUANFENMIMIQIEXIANGGUAN。

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胆结石(Lith)基因图谱

一条垂直线代表一条染色体,着丝粒在顶端。距着丝粒(水平黑线)的遗传距离显示在染色体的左侧。胆结石QTL(Lith基因)和候选基因的位置用水平黑线表示,基因符号在右边(基因符号和名称略)。

YINWEIRENLEIHEXIAOSHURANSETITONGYUANDEYUANYIN,YISHANGZHEIXIELAIZIXIAOSHUDEJIYINYANJIUDUIRENLEIDELithJIYINDEFAXIANYOUZHEZHIDAOXINGDEZUOYONG,BINGCHENGGONGZHENGSHILERENLEIDELITHJIYINABCG5/G8。

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YINCI,GENJUXIAOSHUDELithJIYINTUPU,RENLEIDEGENGDUOLithJIYINJIQIZHIBINGXINGJIZHIJIANGDEYIFAXIANHECHANMING。2010NIAN,YANJIUZHESHOUCITICHULEDANJIESHIBINGDEWUZHONGFABINGYINSU(JIANXIATU):YICHUANYINSUHELithJIYIN;GANDANGUCHUNGAOFENMI,DAOZHIDANGUCHUNGUOBAO(JIGAODANGUCHUNBAOHEZHISHU);DANGUCHUNJIEJINGHEGUTIDANGUCHUNJINGTIDESHENGZHANG;DANNANGYUNDONGSHOUSUN;CHANGDAOYINSU,BAOKUOXISHOUDEDANGUCHUNCONGXIAOCHANGSHUSONGDAOGANZANGYINQIDANZHIGAOFENMI,YIJICHANGDAOWEISHENGWUQUNDEBIANHUA。

五种因素的相互作用示意图:(i)遗传因素和Lith基因;(ii)肝脏高分泌;(iii)胆囊动力低下;(iv)快速相变以及(v)肠道因素。持续性肝胆固醇高分泌是遗传因素调控的结果,导致胆固醇过饱和胆汁的形成,加速胆固醇结晶。胆囊运动功能受损可导致多余粘蛋白凝胶的产生和积累,促进胆泥的形成和微小结石的生长。这些改变也破坏了胆汁酸(肠道因素)的肝肠循环动力学,导致肠道吸收和胆汁酸池的变化。胆固醇吸收的增加将过量胆固醇输送到肝脏,分泌到胆汁中。肠道微生物群的异常可能会破坏肝脏、肠道和胆汁中胆固醇和胆汁酸的代谢,并损害胆囊的排空和再灌注。

KEJIAN,DANGUCHUNJINGTIDEKUAISUSHENGZHANG、JUJIXINGCHENGWEIXIAOJIESHI、ZUIZHONGCHENGSHIZHEIYIJIEGUODOUSHIYOUYUDANGUCHUNGUOBAOHEDAOZHIDE,HAIYOUJIUSHIDANNANGZHANYEDEGAOFENMIYIJIDANNANGSHOUSUNDENINGJIAOXINGCHENG,ZUIZHONGDAOZHILEDANNI(JIDANJIESHIDEQIANTIWU)DEXINGCHENG。

胆结石病理生理学研究最新进展

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结论

SHANGSHUXIAOSHUDANJIESHIYANJIUDECHENGGUOWEIYANJIUTONGYUANRENLEIJIESHIJIYINHETANSUORENLEIDANSHIXINGCHENGDEJIZHIDAKAILEDAMEN。ZAIWEILAIDEYANJIUZHONG,XIAOSHUMOXINGJIANLIHEDANJIESHIYANJIUHEYINGJUJIAOYUHESHOUTI、CHANGDAOWEISHENGWUQUN、XUEZHI、GAOYIDAOSUXUEZHENG、FEIJIUJINGXINGZHIFANGGAN、FEIPANG、TANGNIAOBING、SHUAILAOYIJIBUYUNDONGDESHENGHUOFANGSHIDENGFANGMIANDUIDANJIESHIXINGCHENGDEYINGXIANG。ZHEIXIEXIAOSHUMOXINGSHIYANJIANGWEIGANDANJIBINGDEZHILIAOTIGONGXINDEYIJU。

本文来源:Mouse Models Of Gallstone Disease;Tony Y. Wang/Piero Portincasa著

标签:胆结石模型饲料 上一篇: 下一篇:
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