Objective Atherosclerotic lesions preferentially occur at branch points of arterial trees where the blood flow is disturbed.Disturbed flow increases endothelial permeability,vascular barrier dysfunction,and finally th...Objective Atherosclerotic lesions preferentially occur at branch points of arterial trees where the blood flow is disturbed.Disturbed flow increases endothelial permeability,vascular barrier dysfunction,and finally the development of atherosclerosis.CTRP1,a member of C1q/TNF related protein(CTRP)family,is a novel secreted glycoprotein and its biological functions are largely undefined.展开更多
目的观察人参皂甙Rg1对糖尿病肾病大鼠尿蛋白以及炎症因子肿瘤坏死因子-α(TNF-α)、单核细胞趋化因子蛋白-1(MCP-1)表达的影响。方法将40只雄性SD大鼠随机分为4组:正常对照组、糖尿病模型组、人参皂甙Rg1治疗组、厄贝沙坦(ARB)治疗组...目的观察人参皂甙Rg1对糖尿病肾病大鼠尿蛋白以及炎症因子肿瘤坏死因子-α(TNF-α)、单核细胞趋化因子蛋白-1(MCP-1)表达的影响。方法将40只雄性SD大鼠随机分为4组:正常对照组、糖尿病模型组、人参皂甙Rg1治疗组、厄贝沙坦(ARB)治疗组。采用链脲佐菌素(65mg/kg)腹腔注射建立糖尿病大鼠模型。于动物处死前1d测血糖,用代谢笼收集24h尿液,记录尿量行24h尿蛋白定量和肾功检查。光镜及电镜观察肾组织的病理变化。采用酶联免疫吸附法(ELISA)检测血MCP-1、血及肾TNF-α水平;免疫组织化学检测肾脏组织MCP-1蛋白的表达;实时荧光定量PCR(real-ti me PCR)检测肾脏组织中MCP-1、TNF-α基因水平的表达。结果模型组大鼠镜下见肾小球体积增大,基底膜增厚及系膜物质增多,足细胞较正常对照组减少(P<0.01)。两治疗组与模型组分别比较,肾小球基底膜未见明显增宽,足细胞数增加(P<0.05)。两治疗组之间无明显差异。模型组大鼠血糖、24h尿蛋白、血肌酐水平升高,与对照组相比差异有统计学意义(P<0.05)。两治疗组与模型组相比,血糖水平无明显变化(P>0.05),但24h尿蛋白、血肌酐水平均有所改善(P<0.05)。免疫组织化学、ELISA和real-ti me PCR结果表明,与对照组相比,模型组MCP-1、TNF-α的表达增加(P<0.05),两治疗组MCP-1、TNF-α表达较模型组减少(P<0.05),但两治疗组无明显差异。相关性分析提示MCP-1、TNF-α水平与24h尿蛋白水平(r=0.7802,0.6963)、肾小球硬化指数(r=0.8296,0.7413)、足细胞基底膜厚度(r=0.7678,0.6701)成正相关(P<0.05)。结论人参皂甙Rg1能降低TNF-α、MCP-1的水平,改善糖尿病肾病大鼠足细胞及肾脏的病理损害,能显著减少糖尿病大鼠24h尿蛋白,具有一定的肾保护作用。展开更多
C1q is the first subcomponent of classical pathway in the complement system and a major link between innate and acquired immunities. The globular （gC1q） domain similar with C1q was also found in many non-complement ...C1q is the first subcomponent of classical pathway in the complement system and a major link between innate and acquired immunities. The globular （gC1q） domain similar with C1q was also found in many non-complement C1q-domain-containing （C1qDC） proteins which have similar crystal structure to that of the multifunctional tumor necrosis factor （TNF） ligand family, and also have diverse functions. In this study, we identified a total of 52 independent gene sequences encoding C1q-domain-containing proteins through comprehensive searches of zebrafish genome, cDNA and EST databases. In comparison to 31 orthologous genes in human and different numbers in other species, a significant selective pressure was suggested during vertebrate evolution. Domain organization of C1q-domain-containing （C1qDC） proteins mainly includes a leading signal peptide, a collagen-like region of variable length, and a C-terminal C1q domain. There are 11 highly conserved residues within the C1q domain, among which 2 are invariant within the zebrafish gene set. A more extensive database searches also revealed homologous C1qDC proteins in other vertebrates, invertebrates and even bacterium, but no homologous sequences for encoding C1qDC proteins were found in many species that have a more recent evolutionary history with zebrafish. Therefore, further studies on C1q-domain-containing genes among different species will help us understand evolutionary mechanism of innate and acquired immunities.展开更多
文摘Objective Atherosclerotic lesions preferentially occur at branch points of arterial trees where the blood flow is disturbed.Disturbed flow increases endothelial permeability,vascular barrier dysfunction,and finally the development of atherosclerosis.CTRP1,a member of C1q/TNF related protein(CTRP)family,is a novel secreted glycoprotein and its biological functions are largely undefined.
文摘目的观察人参皂甙Rg1对糖尿病肾病大鼠尿蛋白以及炎症因子肿瘤坏死因子-α(TNF-α)、单核细胞趋化因子蛋白-1(MCP-1)表达的影响。方法将40只雄性SD大鼠随机分为4组:正常对照组、糖尿病模型组、人参皂甙Rg1治疗组、厄贝沙坦(ARB)治疗组。采用链脲佐菌素(65mg/kg)腹腔注射建立糖尿病大鼠模型。于动物处死前1d测血糖,用代谢笼收集24h尿液,记录尿量行24h尿蛋白定量和肾功检查。光镜及电镜观察肾组织的病理变化。采用酶联免疫吸附法(ELISA)检测血MCP-1、血及肾TNF-α水平;免疫组织化学检测肾脏组织MCP-1蛋白的表达;实时荧光定量PCR(real-ti me PCR)检测肾脏组织中MCP-1、TNF-α基因水平的表达。结果模型组大鼠镜下见肾小球体积增大,基底膜增厚及系膜物质增多,足细胞较正常对照组减少(P<0.01)。两治疗组与模型组分别比较,肾小球基底膜未见明显增宽,足细胞数增加(P<0.05)。两治疗组之间无明显差异。模型组大鼠血糖、24h尿蛋白、血肌酐水平升高,与对照组相比差异有统计学意义(P<0.05)。两治疗组与模型组相比,血糖水平无明显变化(P>0.05),但24h尿蛋白、血肌酐水平均有所改善(P<0.05)。免疫组织化学、ELISA和real-ti me PCR结果表明,与对照组相比,模型组MCP-1、TNF-α的表达增加(P<0.05),两治疗组MCP-1、TNF-α表达较模型组减少(P<0.05),但两治疗组无明显差异。相关性分析提示MCP-1、TNF-α水平与24h尿蛋白水平(r=0.7802,0.6963)、肾小球硬化指数(r=0.8296,0.7413)、足细胞基底膜厚度(r=0.7678,0.6701)成正相关(P<0.05)。结论人参皂甙Rg1能降低TNF-α、MCP-1的水平,改善糖尿病肾病大鼠足细胞及肾脏的病理损害,能显著减少糖尿病大鼠24h尿蛋白,具有一定的肾保护作用。
基金Acknowledgements This work was supported by the National Major Basic Research Program （No. 2004CB117401）；by the National Natural Science Foundation of China （No. 90408013）.
文摘C1q is the first subcomponent of classical pathway in the complement system and a major link between innate and acquired immunities. The globular （gC1q） domain similar with C1q was also found in many non-complement C1q-domain-containing （C1qDC） proteins which have similar crystal structure to that of the multifunctional tumor necrosis factor （TNF） ligand family, and also have diverse functions. In this study, we identified a total of 52 independent gene sequences encoding C1q-domain-containing proteins through comprehensive searches of zebrafish genome, cDNA and EST databases. In comparison to 31 orthologous genes in human and different numbers in other species, a significant selective pressure was suggested during vertebrate evolution. Domain organization of C1q-domain-containing （C1qDC） proteins mainly includes a leading signal peptide, a collagen-like region of variable length, and a C-terminal C1q domain. There are 11 highly conserved residues within the C1q domain, among which 2 are invariant within the zebrafish gene set. A more extensive database searches also revealed homologous C1qDC proteins in other vertebrates, invertebrates and even bacterium, but no homologous sequences for encoding C1qDC proteins were found in many species that have a more recent evolutionary history with zebrafish. Therefore, further studies on C1q-domain-containing genes among different species will help us understand evolutionary mechanism of innate and acquired immunities.
