目的:本研究旨在观察转基因扩张型心肌病小鼠心肌组织Acta1、Col3a1基因及蛋白表达变化,探究真武汤防治扩张型心肌病的分子生物学机制。方法:将cT nT R141W基因转入C57BL/6J小鼠,建立了心肌组织特异表达cT nT R141W基因的转基因小鼠模型...目的:本研究旨在观察转基因扩张型心肌病小鼠心肌组织Acta1、Col3a1基因及蛋白表达变化,探究真武汤防治扩张型心肌病的分子生物学机制。方法:将cT nT R141W基因转入C57BL/6J小鼠,建立了心肌组织特异表达cT nT R141W基因的转基因小鼠模型,以C57BL/6J小鼠15只作为空白对照组,模型组小鼠60只,随机分为模型对照组、西药组、中药高剂量组及中药中剂量组,中药组以真武汤高中剂量对模型小鼠治疗4周,卡托普利为阳性对照药物。4周后采用qRT-PCR法检测各组心肌组织Acta1、Col3a1相对表达量; Western Blot法检测各组心肌组织Acta1、Col3a1蛋白表达。结果:与空白对照组比较模型对照组Acta1、Col3a1基因及蛋白表达显著升高(P <0. 01),与模型对照组比较西药组及中药高中剂量组Acta1、Col3a1基因及蛋白表达均显著下降(P <0. 01)。结论:DCM的发病机制与心肌组织中Acta1与Col3a1mRNA及蛋白表达升高有关,真武汤通过下调心肌组织中Acta1与Col3a1 mRNA及蛋白表达,抑制心肌细胞肥大及纤维化过程,起到防治DCM的作用。展开更多
Thoracic aortic dissection(TAD)without familial clustering or syndromic features is known as sporadic TAD(STAD).So far,the genetic basis of STAD remains unknown.Whole exome sequencing was performed in 223 STAD patient...Thoracic aortic dissection(TAD)without familial clustering or syndromic features is known as sporadic TAD(STAD).So far,the genetic basis of STAD remains unknown.Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population(N=637).After population structure and genetic relationship and ancestry analyses,we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD.We found that COL3A1 was significantly relevant to STAD(P=7.35×10^(−6))after 10000 times permutation test(P=2.49×10^(−3)).Moreover,another independent cohort,including 423 cases and 734 non-STAD subjects(N=1157),replicated our results(P=0.021).Further bioinformatics analysis showed that COL3A1 was highly expressed in dissected aortic tissues,and its expression was related to the extracellular matrix(ECM)pathway.Our study identified a profile of known heritable TAD genes in the Chinese STAD population and found that COL3A1 could increase the risk of STAD through the ECM pathway.We wanted to expand the knowledge of the genetic basis and pathology of STAD,which may further help in providing better genetic counseling to the patients.展开更多
文摘目的:本研究旨在观察转基因扩张型心肌病小鼠心肌组织Acta1、Col3a1基因及蛋白表达变化,探究真武汤防治扩张型心肌病的分子生物学机制。方法:将cT nT R141W基因转入C57BL/6J小鼠,建立了心肌组织特异表达cT nT R141W基因的转基因小鼠模型,以C57BL/6J小鼠15只作为空白对照组,模型组小鼠60只,随机分为模型对照组、西药组、中药高剂量组及中药中剂量组,中药组以真武汤高中剂量对模型小鼠治疗4周,卡托普利为阳性对照药物。4周后采用qRT-PCR法检测各组心肌组织Acta1、Col3a1相对表达量; Western Blot法检测各组心肌组织Acta1、Col3a1蛋白表达。结果:与空白对照组比较模型对照组Acta1、Col3a1基因及蛋白表达显著升高(P <0. 01),与模型对照组比较西药组及中药高中剂量组Acta1、Col3a1基因及蛋白表达均显著下降(P <0. 01)。结论:DCM的发病机制与心肌组织中Acta1与Col3a1mRNA及蛋白表达升高有关,真武汤通过下调心肌组织中Acta1与Col3a1 mRNA及蛋白表达,抑制心肌细胞肥大及纤维化过程,起到防治DCM的作用。
基金This work was supported by the National Natural Science Foundation of China(Nos.91839302,91439203,and 81700413)the National Key R&D Program of China(No.2017YFC0909400)the Municipal Science and Technology Major Project(No.2017SHZDZX01).
文摘Thoracic aortic dissection(TAD)without familial clustering or syndromic features is known as sporadic TAD(STAD).So far,the genetic basis of STAD remains unknown.Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population(N=637).After population structure and genetic relationship and ancestry analyses,we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD.We found that COL3A1 was significantly relevant to STAD(P=7.35×10^(−6))after 10000 times permutation test(P=2.49×10^(−3)).Moreover,another independent cohort,including 423 cases and 734 non-STAD subjects(N=1157),replicated our results(P=0.021).Further bioinformatics analysis showed that COL3A1 was highly expressed in dissected aortic tissues,and its expression was related to the extracellular matrix(ECM)pathway.Our study identified a profile of known heritable TAD genes in the Chinese STAD population and found that COL3A1 could increase the risk of STAD through the ECM pathway.We wanted to expand the knowledge of the genetic basis and pathology of STAD,which may further help in providing better genetic counseling to the patients.
