目的:探讨醛固酮瘤中CYP11B2,CYP11B1基因多态性与CYP11B2基因mRNA表达及术前血浆醛固酮浓度、收缩压、舒张压等临床表型的关系。方法:20例正常肾上腺和69例醛固酮瘤组织标本,分别取自2006年5月～2007年11月在华中科技大学同济医学院附...目的:探讨醛固酮瘤中CYP11B2,CYP11B1基因多态性与CYP11B2基因mRNA表达及术前血浆醛固酮浓度、收缩压、舒张压等临床表型的关系。方法:20例正常肾上腺和69例醛固酮瘤组织标本,分别取自2006年5月～2007年11月在华中科技大学同济医学院附属同济医院泌尿外科行肾癌根治术和肾上腺手术切除的患者。采用Taqman探针法检测DNA多态性,包括CYP11B2基因的rs1799998、rs4539及CYP11B1基因的rs6410和rs6387;采用两对独立的PCR检测CYP11B2基因intron2多态性(野生型/转位型)。采用syb greenReal time RT-PCR检测CYP11B2基因mRNA表达。在Rstatistics program 2.7.0程序包中使用SNPassoc 1.5-3和Haplo.stats 1.3.8分析CYP11B2和CYP11B1基因多态性及单体型与CYP11B2基因表达量和血浆醛固酮浓度、收缩压、舒张压等临床表型的关系。结果:单体型分型中,Global Score统计显示:CYP11B2-CYP11B1单体型与CYP11B2mRNA表达量增加相关(global-stat=16.175,df=8,P=0.04),与血清醛固酮水平相关(global-stat=20.407,df=8,P=0.009)。但与收缩压和舒张压不相关(分别P=0.34,P=0.54);多元回归分析中发现单体型H1(AGAConvT)和H3(AGAWtC)与CYP11B2基因mRNA的表达上调相关(经过Bonferroni校正后分别P=0.002;P=0.003),而H6(AGGWtT)、H10(AAAWtT)和H16(GAAWtT)与过多的醛固酮分泌相关(经过Bonferroni校正后分别P<0.0005;P=0.002;P=0.0015);但未见有单体型与收缩压和舒张压相关(均P>0.05)。结论:CYP11B2和CYP11B1基因多态性可能通过上调CYP11B2的表达,导致醛固酮瘤患者血清醛固酮水平的升高。展开更多
identify aldosterone synthase gene CYP11B2 mRNA expression in normal and fibrotic liver in rats and evaluate the curative effect of antisterone Methods 160 Wistar rats weighing about 250?g were divided into 4 grou...identify aldosterone synthase gene CYP11B2 mRNA expression in normal and fibrotic liver in rats and evaluate the curative effect of antisterone Methods 160 Wistar rats weighing about 250?g were divided into 4 groups In the model group (n=40), the rats were injected with 40% CCl 4 (0 25?ml/100?g) subcutaneously three times a week In the antisterone group (n=40), the rats were injected with 40% CCl 4 (0 25?ml/100?g) subcutaneously three times a week Antisterone equivalent to 20?mg·kg 1 ·d 1 was given intragastrically (ig) In the malotilate group (n=40), the rats were injected with 40% CCl 4 (0 25?ml/100?g) subcutaneously three times a week Malotilate equivalent to 50?mg·kg 1 ·d 1 was given ig In the control group (n=40), the rats were injected with olive oil only After 2,4,6,8 and 10 weeks, animals were sacrificed, and morphological examination was carried out The area of collagen was examined with an Image Analyse System Expression of the aldosterone synthase gene, CYP11B2 mRNA, in fibrotic and normal liver was detected by means of reverse transcriptase polymerase chain reaction (RT PCR) and in situ hybridization Results In situ hybridization and RT PCR showed that the expression of CYP11B2 mRNA, which localized in the endoplasm of hepatic stellate cells (HSCs), was up regulated when fibrogenesis occurred Histological observation indicated that the grade of fibrosis and the area of collagen in the antisterone group were less than those in model group before 6 weeks ( P <0 05) There was no significant difference between the antisterone and malotilate groups ( P >0 05) After that, however, the grade of fibrosis and the area of collagen in the antisterone group were higher than those in the malotilate group ( P <0 05) There was no significant difference between the antisterone and model groups ( P >0 05) Conclusions The expression of CYP11B2 mRNA is up regulated in fibrotic liver Antisterone can have a partial fibrogenesis inhibiting effect in the early stages展开更多
文摘目的:探讨醛固酮瘤中CYP11B2,CYP11B1基因多态性与CYP11B2基因mRNA表达及术前血浆醛固酮浓度、收缩压、舒张压等临床表型的关系。方法:20例正常肾上腺和69例醛固酮瘤组织标本,分别取自2006年5月～2007年11月在华中科技大学同济医学院附属同济医院泌尿外科行肾癌根治术和肾上腺手术切除的患者。采用Taqman探针法检测DNA多态性,包括CYP11B2基因的rs1799998、rs4539及CYP11B1基因的rs6410和rs6387;采用两对独立的PCR检测CYP11B2基因intron2多态性(野生型/转位型)。采用syb greenReal time RT-PCR检测CYP11B2基因mRNA表达。在Rstatistics program 2.7.0程序包中使用SNPassoc 1.5-3和Haplo.stats 1.3.8分析CYP11B2和CYP11B1基因多态性及单体型与CYP11B2基因表达量和血浆醛固酮浓度、收缩压、舒张压等临床表型的关系。结果:单体型分型中,Global Score统计显示:CYP11B2-CYP11B1单体型与CYP11B2mRNA表达量增加相关(global-stat=16.175,df=8,P=0.04),与血清醛固酮水平相关(global-stat=20.407,df=8,P=0.009)。但与收缩压和舒张压不相关(分别P=0.34,P=0.54);多元回归分析中发现单体型H1(AGAConvT)和H3(AGAWtC)与CYP11B2基因mRNA的表达上调相关(经过Bonferroni校正后分别P=0.002;P=0.003),而H6(AGGWtT)、H10(AAAWtT)和H16(GAAWtT)与过多的醛固酮分泌相关(经过Bonferroni校正后分别P<0.0005;P=0.002;P=0.0015);但未见有单体型与收缩压和舒张压相关(均P>0.05)。结论:CYP11B2和CYP11B1基因多态性可能通过上调CYP11B2的表达,导致醛固酮瘤患者血清醛固酮水平的升高。
基金theNationalNaturalScienceFoundationofChina (No 39870 331)
文摘identify aldosterone synthase gene CYP11B2 mRNA expression in normal and fibrotic liver in rats and evaluate the curative effect of antisterone Methods 160 Wistar rats weighing about 250?g were divided into 4 groups In the model group (n=40), the rats were injected with 40% CCl 4 (0 25?ml/100?g) subcutaneously three times a week In the antisterone group (n=40), the rats were injected with 40% CCl 4 (0 25?ml/100?g) subcutaneously three times a week Antisterone equivalent to 20?mg·kg 1 ·d 1 was given intragastrically (ig) In the malotilate group (n=40), the rats were injected with 40% CCl 4 (0 25?ml/100?g) subcutaneously three times a week Malotilate equivalent to 50?mg·kg 1 ·d 1 was given ig In the control group (n=40), the rats were injected with olive oil only After 2,4,6,8 and 10 weeks, animals were sacrificed, and morphological examination was carried out The area of collagen was examined with an Image Analyse System Expression of the aldosterone synthase gene, CYP11B2 mRNA, in fibrotic and normal liver was detected by means of reverse transcriptase polymerase chain reaction (RT PCR) and in situ hybridization Results In situ hybridization and RT PCR showed that the expression of CYP11B2 mRNA, which localized in the endoplasm of hepatic stellate cells (HSCs), was up regulated when fibrogenesis occurred Histological observation indicated that the grade of fibrosis and the area of collagen in the antisterone group were less than those in model group before 6 weeks ( P <0 05) There was no significant difference between the antisterone and malotilate groups ( P >0 05) After that, however, the grade of fibrosis and the area of collagen in the antisterone group were higher than those in the malotilate group ( P <0 05) There was no significant difference between the antisterone and model groups ( P >0 05) Conclusions The expression of CYP11B2 mRNA is up regulated in fibrotic liver Antisterone can have a partial fibrogenesis inhibiting effect in the early stages
