本研究以湖羊肝脏为材料对肝受体类似物-1(Liver receptor homolog-1,Lrh-1;NR5A2)基因序列进行RT-PCR和RACE测定,并用DNAman、Tmpred、Signal P 3.0、Expasy等生物信息学分析软件和在线工具,对Lrh-1cDNA序列及其蛋白的理化特性、跨膜...本研究以湖羊肝脏为材料对肝受体类似物-1(Liver receptor homolog-1,Lrh-1;NR5A2)基因序列进行RT-PCR和RACE测定,并用DNAman、Tmpred、Signal P 3.0、Expasy等生物信息学分析软件和在线工具,对Lrh-1cDNA序列及其蛋白的理化特性、跨膜结构、信号肽和二级结构进行生物信息学分析,同时采用实时荧光定量PCR方法检测湖羊Lrh-1基因的组织表达谱。结果表明,湖羊Lrh-1基因cDNA序列全长1 488bp,与牛的核酸序列相似度最高,为98%,编码区共编码495个氨基酸,氨基酸序列与牛、人、马、猴、犬、小鼠、褐鼠的氨基酸同源性分别为98%、97%、96%、97%、97%、86%和86%;Lrh-1mRNA在湖羊脑、消化及生殖系统组织中均有表达且具有组织特异性,其中在下丘脑组织中的表达量相对最高。展开更多
目的研究胆囊胆固醇结石患者肝脏的核受体基因:肝脏X受体α(liver X receptor α,LXRα)、法尼醇受体(farnesoid X receptor,FXR)、人类固醇异生物受体(steroid xenobiotic receptor,SXR)及肝受体同类物1(liver receptor homolog 1,LRH...目的研究胆囊胆固醇结石患者肝脏的核受体基因:肝脏X受体α(liver X receptor α,LXRα)、法尼醇受体(farnesoid X receptor,FXR)、人类固醇异生物受体(steroid xenobiotic receptor,SXR)及肝受体同类物1(liver receptor homolog 1,LRH-1)的表达,探讨胆固醇结石病的发病机理。方法27例胆囊胆固醇结石患者(胆石组),男6例,女21例,平均年龄(52.44±1.92)岁。10例无胆石症的胆囊息肉患者为对照(对照组),男6例,女4例,平均年龄(47.10±2.73)岁。测定胆石胆固醇成分及血清脂类成分:总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-ch)、载脂蛋白(Apo)B和ApoA1和胆汁脂类成分(胆固醇、磷脂和胆汁酸),并计算胆汁总脂和胆汁胆固醇饱和指数。实时定量PCR法测定肝脏LRH-1、FXR、SXR及LXRα基因的表达量。结果胆石组血清中HDL-ch浓度明显低于对照组〔(0.93±0.05)mmol/L vs(1.33±0.09)mmol/L〕,P<0.001;ApoA1浓度也低于对照组〔(1.19±0.05)g/L vs(1.36±0.06)g/L〕,P<0.05;血清ApoB、TC和TG2组比较差异均无统计学意义(P>0.05)。胆石组胆汁呈胆固醇过饱和(胆固醇过饱和指数:1.17±0.02 vs 0.79±0.10,P<0.001);胆汁胆固醇摩尔百分比浓度较对照组升高〔(7.96±0.39)mol% vs(5.26±0.89)mol%〕,P<0.01;胆汁总脂较对照组明显下降〔(104.72±10.51)g/L vs(154.24±14.20)g/L〕,P<0.05;胆汁中胆汁酸和磷脂成分2组比较差异均无统计学意义(P>0.05)。胆石组LRH-1表达高于对照组(14.18±1.80 vs 7.22±2.22),P<0.05,LXRα、FXR和SXR表达2组差异无统计学意义(P>0.05)。结论人类肝脏LRH-1的表达增高与胆囊胆固醇结石形成有关。展开更多
目的通过胆固醇结石（GS）小鼠肝脏的核受体基因—肝核受体类似物1（1iver receptor homolog 1,LRH-1）、法尼醇受体（farnesoid X receptor,FXR）、类固醇受体（steroid X receptor,SXR）的表达,探讨与胆固醇结石形成关系.方法 C57BL/...目的通过胆固醇结石（GS）小鼠肝脏的核受体基因—肝核受体类似物1（1iver receptor homolog 1,LRH-1）、法尼醇受体（farnesoid X receptor,FXR）、类固醇受体（steroid X receptor,SXR）的表达,探讨与胆固醇结石形成关系.方法 C57BL/6雌性小鼠40只,平均出生后10周,重量28-35g,20只一组分为两组,一组予以正常饮食另一组予以高脂饮食喂养,均8周后处死.病理切片检查胆囊壁细胞组织学改变,并分别采用实时定量RT-PCR法和Western Blot法测定肝脏LRH-I、FXR、SXR的mRNA表达.结果胆固醇结石小鼠胆囊壁细胞呈现炎性改变,LRH-I的mRNA表达均高于对照组（P〈0.01）,FXR、SXR的mRNA表达两组差异无统计学意义.结论啮齿动物肝脏LRH-1基因的表达异常与胆固醇结石形成有关,FXR、SXR基因的表达与胆固醇结石形成可能无关.展开更多
Hormone replacement therapy is necessary for patients with adrenal and gonadal failure.Steroid hormone treatment is also employed in aging people for sex hormone deficiency.These patients undergo such therapies,which ...Hormone replacement therapy is necessary for patients with adrenal and gonadal failure.Steroid hormone treatment is also employed in aging people for sex hormone deficiency.These patients undergo such therapies,which have associated risks,for their entire life.Stem cells represent an innovative tool for tissue regeneration and the possibility of solving these problems.Among various stem cell types,mesenchymal stem cells have the potential to differentiate into steroidogenic cells both in vivo and in vitro.In particular,they can effectively be differentiated into steroidogenic cells by expressing nuclear receptor 5A subfamily proteins(steroidogenic factor-1 and liver receptor homolog-1)with the aid of cAMP.This approach will provide a source of cells for future regenerative medicine for the treatment of diseases caused by steroidogenesis deficiencies.It can also represent a useful tool for studying the molecular mechanisms of steroidogenesis and its related diseases.展开更多
文摘目的:探讨胆固醇结石(GS)小鼠肝脏的核受体基因——肝核受体类似物1(liver receptor homolog 1,LRH-1)及其调控基因胆固醇7α-羟化酶(cholesterol 7-αhydroxylase,CYP7A1)的表达。方法:雌性C57BL/6小鼠40只,分为2组,每组20只,分别予以正常饮食、高脂饮食喂养10周后处死。病理切片检查小鼠胆囊壁细胞组织学改变,实时定量PCR法测定肝脏LRH-1及CYP7A1表达量。Western Blot方法测定肝脏上述基因蛋白的表达量。结果:胆结石小鼠胆囊壁细胞呈现炎性改变。胆石组小鼠LRH-1 m RNA及蛋白表达均高于对照组(P<0.01),CYP7A1 m RNA及蛋白表达量较对照组升高(P<0.01)。结论:啮齿动物肝脏LRH-1和CYP7A1的表达异常与胆囊胆固醇结石形成有关,可能共同在小鼠胆结石形成中发挥作用。
文摘目的研究胆囊胆固醇结石患者肝脏的核受体基因:肝脏X受体α(liver X receptor α,LXRα)、法尼醇受体(farnesoid X receptor,FXR)、人类固醇异生物受体(steroid xenobiotic receptor,SXR)及肝受体同类物1(liver receptor homolog 1,LRH-1)的表达,探讨胆固醇结石病的发病机理。方法27例胆囊胆固醇结石患者(胆石组),男6例,女21例,平均年龄(52.44±1.92)岁。10例无胆石症的胆囊息肉患者为对照(对照组),男6例,女4例,平均年龄(47.10±2.73)岁。测定胆石胆固醇成分及血清脂类成分:总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-ch)、载脂蛋白(Apo)B和ApoA1和胆汁脂类成分(胆固醇、磷脂和胆汁酸),并计算胆汁总脂和胆汁胆固醇饱和指数。实时定量PCR法测定肝脏LRH-1、FXR、SXR及LXRα基因的表达量。结果胆石组血清中HDL-ch浓度明显低于对照组〔(0.93±0.05)mmol/L vs(1.33±0.09)mmol/L〕,P<0.001;ApoA1浓度也低于对照组〔(1.19±0.05)g/L vs(1.36±0.06)g/L〕,P<0.05;血清ApoB、TC和TG2组比较差异均无统计学意义(P>0.05)。胆石组胆汁呈胆固醇过饱和(胆固醇过饱和指数:1.17±0.02 vs 0.79±0.10,P<0.001);胆汁胆固醇摩尔百分比浓度较对照组升高〔(7.96±0.39)mol% vs(5.26±0.89)mol%〕,P<0.01;胆汁总脂较对照组明显下降〔(104.72±10.51)g/L vs(154.24±14.20)g/L〕,P<0.05;胆汁中胆汁酸和磷脂成分2组比较差异均无统计学意义(P>0.05)。胆石组LRH-1表达高于对照组(14.18±1.80 vs 7.22±2.22),P<0.05,LXRα、FXR和SXR表达2组差异无统计学意义(P>0.05)。结论人类肝脏LRH-1的表达增高与胆囊胆固醇结石形成有关。
文摘目的通过胆固醇结石（GS）小鼠肝脏的核受体基因—肝核受体类似物1（1iver receptor homolog 1,LRH-1）、法尼醇受体（farnesoid X receptor,FXR）、类固醇受体（steroid X receptor,SXR）的表达,探讨与胆固醇结石形成关系.方法 C57BL/6雌性小鼠40只,平均出生后10周,重量28-35g,20只一组分为两组,一组予以正常饮食另一组予以高脂饮食喂养,均8周后处死.病理切片检查胆囊壁细胞组织学改变,并分别采用实时定量RT-PCR法和Western Blot法测定肝脏LRH-I、FXR、SXR的mRNA表达.结果胆固醇结石小鼠胆囊壁细胞呈现炎性改变,LRH-I的mRNA表达均高于对照组（P〈0.01）,FXR、SXR的mRNA表达两组差异无统计学意义.结论啮齿动物肝脏LRH-1基因的表达异常与胆固醇结石形成有关,FXR、SXR基因的表达与胆固醇结石形成可能无关.
基金Supported by Ministry of Education,Culture,Sports,Science and Technology of Japan,No.23590329the Terumo Life Science Foundationthe Smoking Research Foundation
文摘Hormone replacement therapy is necessary for patients with adrenal and gonadal failure.Steroid hormone treatment is also employed in aging people for sex hormone deficiency.These patients undergo such therapies,which have associated risks,for their entire life.Stem cells represent an innovative tool for tissue regeneration and the possibility of solving these problems.Among various stem cell types,mesenchymal stem cells have the potential to differentiate into steroidogenic cells both in vivo and in vitro.In particular,they can effectively be differentiated into steroidogenic cells by expressing nuclear receptor 5A subfamily proteins(steroidogenic factor-1 and liver receptor homolog-1)with the aid of cAMP.This approach will provide a source of cells for future regenerative medicine for the treatment of diseases caused by steroidogenesis deficiencies.It can also represent a useful tool for studying the molecular mechanisms of steroidogenesis and its related diseases.
