目的分析1例Blake’s陷窝囊肿合并小脑蚓部发育不良的遗传学病因。方法收集胎儿B超、MRI、尸检、染色体核型分析、CNV-seq检查以及全外显子组测序结果,并利用Sanger测序对致病变异位点进行确认。检索The Human Protein Atlas数据库、Mon...目的分析1例Blake’s陷窝囊肿合并小脑蚓部发育不良的遗传学病因。方法收集胎儿B超、MRI、尸检、染色体核型分析、CNV-seq检查以及全外显子组测序结果,并利用Sanger测序对致病变异位点进行确认。检索The Human Protein Atlas数据库、Monarch数据库以及Simple ClinVar数据库,分析候选致病基因与疾病的关系。构建致病基因野生型以及变异型蛋白3D结构,利用Gromacs软件对野生型和变异型致病基因蛋白进行分子动力学模拟。结果胎儿在23周、25周以及28周依次出现Blake’s囊肿、小脑发育不良、双侧侧脑室室管膜下囊肿。羊水染色体核型分析以及CNV-seq结果未见异常。全外显子组测序显示胎儿VLDLR复合杂合变异:c.262C>T(p.R88*)和c.670G>A(p.E224K)。这两个未见报道的可能致病性变异分别遗传自父、母亲,且均位于VLDLR的LDL受体A家族结构域。c.670G>A(p.E224K)可以影响VLDLR的RMSD、Gyrate、蛋白内氢键数量以及第225氨基酸位置的二级结构。结论VLDLR基因c.262C>T(p.R88*)和c.670G>A(p.E224K)复合杂合变异是导致Blake’s陷窝囊肿合并小脑蚓部发育不良的病因。展开更多
Very low-density lipoprotein receptor (VLDLR) is the major receptor with which cells can uptake the triacylglycerol from blood. It is divided into two subtypes according to presence of O- linked sugar domain located ...Very low-density lipoprotein receptor (VLDLR) is the major receptor with which cells can uptake the triacylglycerol from blood. It is divided into two subtypes according to presence of O- linked sugar domain located in the VLDLR receptor immediately outside of the membrane. Type Ⅰ VLDLR contains the O-link domain, while type Ⅱhas no such domain. The type ⅠVLDLR are mainly found on the surface of human myocardial cells. The result of our quantitative polymerase chain reaction on the normal and fibrotic cardiac muscles showed that both subtypes and expression level of VLDLR on the myocardial cell surface did not vary significantly between the normal and the fibrotic cardiac muscles despite the presence of malfunction due to fibrosis. This finding suggests that fibrosis doesn't exert significant influence on the subtype and the expression of VLDLR on the sur- face of myocardial cells. Such inconsistence with the changes found in other fibrotic tissues is awaiting further studies.展开更多
AIM:To explore whether the retinal neovascularization(NV)in a genetic mutant mice model could be ameliorated in an inherited retinitis pigmentosa(RP)mouse,which would help to elucidate the possible mechanism and preve...AIM:To explore whether the retinal neovascularization(NV)in a genetic mutant mice model could be ameliorated in an inherited retinitis pigmentosa(RP)mouse,which would help to elucidate the possible mechanism and prevention of retinal NV diseases in clinic.METHODS:The Vldlr^(-/-)mice,the genetic mutant mouse model of retinal NV caused by the homozygous mutation of Vldlr gene,with the rd1 mice,the inherited RP mouse caused by homozygous mutation of Pde6b gene were bred.Intercrossing of the above two mice led to the birth of the F1 hybrids,further inbreeding of which gave birth to the F2 offspring.The ocular genotypes and phenotypes of the mice from all generations were examined,with the F2 offspring grouped according to the genotypes.RESULTS:The rd1 mice exhibited the RP phenotype of outer retinal degeneration and loss of retinal function.The Vldlr^(-/-)mice exhibited the phenotype of retinal NV obviously shown by the fundus fluorescein angiography.The F1 hydrides,with the heterozygote genotype,exhibited no phenotypes of RP or retinal NV.The F2 offspring with homozygous genotypes were grouped into four subgroups.They were the F2-Ⅰmice with the wild-type Pde6b and Vldlr genes(Pde6b~(+/+)-Vldlr~(+/+)),which had normal ocular phenotypes;the F2-Ⅱmice with homozygous mutant Vldlr gene(Pde6b~(+/+)-Vldlr^(-/-)),which exhibited the retinal NV phenotype;the F2-Ⅲmice with homozygous mutant Pde6b gene(Pde6b^(-/-)-Vldlr~(+/+)),which exhibited the RP phenotype.Specifically,the F2-Ⅳmice with homozygous mutant Vldlr and Pde6b gene(Pde6b^(-/-)-Vldlr^(-/-))showed only the RP phenotype,without the signs of retinal NV.CONCLUSION:The retinal NV can be inhibited by the RP phenotype,which implies the role of a hyperoxic state in treating retinal NV diseases.展开更多
目的:考察济阴颗粒对雌性冠心病大鼠脂代谢通路因子小窝蛋白1(caveolin-1,Cav-1)、低密度脂蛋白受体(low density lipoprotein receptor,LDLR)、极低密度脂蛋白受体(very low density lipoprotein receptor,VLDLR)、ATP结合盒转运蛋白...目的:考察济阴颗粒对雌性冠心病大鼠脂代谢通路因子小窝蛋白1(caveolin-1,Cav-1)、低密度脂蛋白受体(low density lipoprotein receptor,LDLR)、极低密度脂蛋白受体(very low density lipoprotein receptor,VLDLR)、ATP结合盒转运蛋白家族转运蛋白A1(atp-binding cassette transporter a1,ABCA1)、载脂蛋白A1(apolipoprotein-a1,ApoA1)、B1类清道夫受体(scavenger receptor class B type1,SRB1)mRNA水平、血清总胆固醇含量的影响。方法:健康雌性SD大鼠75只,除空白组15只外,其余60只制备绝经期冠心病模型,分为模型组、西药对照组、中药对照组、济阴颗粒组,每组15只。分离心脏主动脉,Elisa法测定各组大鼠血清总胆固醇含量,实时定量PCR方法检测雌性冠心病大鼠CAV1、LDLR、VLDLR、ABCA1、ApoA1、SRB1 mRNA水平。结果:实时定量PCR结果显示,同模型组比较,空白组、西药阳性组、中药阳性组、济阴颗粒组ABCA1、ApoA1、CAV1、LDLR、SRB1、VLDLR mRNA表达增加,差异有统计学意义(P<0.05)。与空白组相比,济阴颗粒组ApoA1、CAV1、SRB1、VLDLR mRNA表达明显减少,差异有统计学意义(P<0.01),济阴颗粒组ABCA1、LDLR mRNA表达差异无统计学意义。ELISA结果显示,与模型组比较,空白组、西药阳性组、中药阳性组总胆固醇含量显著减少,差异有统计学意义(P<0.01),济阴颗粒组总胆固醇含量减少,具有统计学意义(P<0.05)。结论:济阴颗粒可能通过降低去卵巢雌性冠心病大鼠总胆固醇含量,提高ABCA1、ApoA1、CAV1、LDLR、SRB1、VLDLR mRNA相对表达量来改善雌性大鼠冠心病。展开更多
文摘目的分析1例Blake’s陷窝囊肿合并小脑蚓部发育不良的遗传学病因。方法收集胎儿B超、MRI、尸检、染色体核型分析、CNV-seq检查以及全外显子组测序结果,并利用Sanger测序对致病变异位点进行确认。检索The Human Protein Atlas数据库、Monarch数据库以及Simple ClinVar数据库,分析候选致病基因与疾病的关系。构建致病基因野生型以及变异型蛋白3D结构,利用Gromacs软件对野生型和变异型致病基因蛋白进行分子动力学模拟。结果胎儿在23周、25周以及28周依次出现Blake’s囊肿、小脑发育不良、双侧侧脑室室管膜下囊肿。羊水染色体核型分析以及CNV-seq结果未见异常。全外显子组测序显示胎儿VLDLR复合杂合变异:c.262C>T(p.R88*)和c.670G>A(p.E224K)。这两个未见报道的可能致病性变异分别遗传自父、母亲,且均位于VLDLR的LDL受体A家族结构域。c.670G>A(p.E224K)可以影响VLDLR的RMSD、Gyrate、蛋白内氢键数量以及第225氨基酸位置的二级结构。结论VLDLR基因c.262C>T(p.R88*)和c.670G>A(p.E224K)复合杂合变异是导致Blake’s陷窝囊肿合并小脑蚓部发育不良的病因。
文摘Very low-density lipoprotein receptor (VLDLR) is the major receptor with which cells can uptake the triacylglycerol from blood. It is divided into two subtypes according to presence of O- linked sugar domain located in the VLDLR receptor immediately outside of the membrane. Type Ⅰ VLDLR contains the O-link domain, while type Ⅱhas no such domain. The type ⅠVLDLR are mainly found on the surface of human myocardial cells. The result of our quantitative polymerase chain reaction on the normal and fibrotic cardiac muscles showed that both subtypes and expression level of VLDLR on the myocardial cell surface did not vary significantly between the normal and the fibrotic cardiac muscles despite the presence of malfunction due to fibrosis. This finding suggests that fibrosis doesn't exert significant influence on the subtype and the expression of VLDLR on the sur- face of myocardial cells. Such inconsistence with the changes found in other fibrotic tissues is awaiting further studies.
基金Supported by the Pilot Project of Fujian Province(No.2016Y0067,No.2020Y0076,No.2020J05282)the Foundation of Key Research Plan of Shaanxi Province(No.2018SF-257)the Scientific Research Project of the 900th Hospital of Joint Logistic Support Force,PLA of 2018(No.2018Q02)。
文摘AIM:To explore whether the retinal neovascularization(NV)in a genetic mutant mice model could be ameliorated in an inherited retinitis pigmentosa(RP)mouse,which would help to elucidate the possible mechanism and prevention of retinal NV diseases in clinic.METHODS:The Vldlr^(-/-)mice,the genetic mutant mouse model of retinal NV caused by the homozygous mutation of Vldlr gene,with the rd1 mice,the inherited RP mouse caused by homozygous mutation of Pde6b gene were bred.Intercrossing of the above two mice led to the birth of the F1 hybrids,further inbreeding of which gave birth to the F2 offspring.The ocular genotypes and phenotypes of the mice from all generations were examined,with the F2 offspring grouped according to the genotypes.RESULTS:The rd1 mice exhibited the RP phenotype of outer retinal degeneration and loss of retinal function.The Vldlr^(-/-)mice exhibited the phenotype of retinal NV obviously shown by the fundus fluorescein angiography.The F1 hydrides,with the heterozygote genotype,exhibited no phenotypes of RP or retinal NV.The F2 offspring with homozygous genotypes were grouped into four subgroups.They were the F2-Ⅰmice with the wild-type Pde6b and Vldlr genes(Pde6b~(+/+)-Vldlr~(+/+)),which had normal ocular phenotypes;the F2-Ⅱmice with homozygous mutant Vldlr gene(Pde6b~(+/+)-Vldlr^(-/-)),which exhibited the retinal NV phenotype;the F2-Ⅲmice with homozygous mutant Pde6b gene(Pde6b^(-/-)-Vldlr~(+/+)),which exhibited the RP phenotype.Specifically,the F2-Ⅳmice with homozygous mutant Vldlr and Pde6b gene(Pde6b^(-/-)-Vldlr^(-/-))showed only the RP phenotype,without the signs of retinal NV.CONCLUSION:The retinal NV can be inhibited by the RP phenotype,which implies the role of a hyperoxic state in treating retinal NV diseases.
文摘目的:考察济阴颗粒对雌性冠心病大鼠脂代谢通路因子小窝蛋白1(caveolin-1,Cav-1)、低密度脂蛋白受体(low density lipoprotein receptor,LDLR)、极低密度脂蛋白受体(very low density lipoprotein receptor,VLDLR)、ATP结合盒转运蛋白家族转运蛋白A1(atp-binding cassette transporter a1,ABCA1)、载脂蛋白A1(apolipoprotein-a1,ApoA1)、B1类清道夫受体(scavenger receptor class B type1,SRB1)mRNA水平、血清总胆固醇含量的影响。方法:健康雌性SD大鼠75只,除空白组15只外,其余60只制备绝经期冠心病模型,分为模型组、西药对照组、中药对照组、济阴颗粒组,每组15只。分离心脏主动脉,Elisa法测定各组大鼠血清总胆固醇含量,实时定量PCR方法检测雌性冠心病大鼠CAV1、LDLR、VLDLR、ABCA1、ApoA1、SRB1 mRNA水平。结果:实时定量PCR结果显示,同模型组比较,空白组、西药阳性组、中药阳性组、济阴颗粒组ABCA1、ApoA1、CAV1、LDLR、SRB1、VLDLR mRNA表达增加,差异有统计学意义(P<0.05)。与空白组相比,济阴颗粒组ApoA1、CAV1、SRB1、VLDLR mRNA表达明显减少,差异有统计学意义(P<0.01),济阴颗粒组ABCA1、LDLR mRNA表达差异无统计学意义。ELISA结果显示,与模型组比较,空白组、西药阳性组、中药阳性组总胆固醇含量显著减少,差异有统计学意义(P<0.01),济阴颗粒组总胆固醇含量减少,具有统计学意义(P<0.05)。结论:济阴颗粒可能通过降低去卵巢雌性冠心病大鼠总胆固醇含量,提高ABCA1、ApoA1、CAV1、LDLR、SRB1、VLDLR mRNA相对表达量来改善雌性大鼠冠心病。
