糖/血小板反应素-1/转化生长因子β1信号传导途径在糖尿病心肌病发病中的作用

目的探讨糖／血小板反应素-1（TSP-1）／转化生长因子（TGF）B。信号传导途径在糖尿病心肌病发病中的作用。方法采用高脂高热量饮食诱导出胰岛素抵抗,加小剂量链脲佐菌素注射建立糖尿病心肌病动物模型,以Masson染色、实时定量逆转录-聚合酶链反应、Western blot技术,检测左室心肌胶原含量、TSP-1、TGFβ1 mRNA和蛋白质表达水平的变化。结果与对照组相比,糖尿病心肌病大鼠左室心肌组织胶原含量明显高,存在心肌间质纤维化;TSP-1 mRNA和蛋白质表达均明显高,TGFβ1 mRNA、活性和非活性TGFβ1蛋白质表达亦明显高;TSP-1、TGFβ1 mRNA水平与空腹血糖、心肌组织胶原含量以及左室舒张功能指标均明显相关,TSP-1、活性TGFβ1蛋白质表达水平与空腹血糖、心肌组织胶原含量以及左室舒张功能指标之间亦存在明显的相关关系,但非活性TGFβ1蛋白质表达水平与空腹血糖、心肌组织胶原含量以及左室舒张功能指标之间无相关性。结论糖／TSP-1／TGFβ1信号传导途径在糖尿病心肌病时心肌间质纤维化发生发展过程中可能起着重要的作用,为临床上糖尿病心肌病的治疗提供了新的靶点。     

转化生长因子β1与糖尿病心肌病关系的实验研究

目的 观察链脲佐菌素（STZ）实验性糖尿病大鼠心肌转化生长因子β1（TGF－β1）、纤维连接蛋白（FN）、层粘连蛋白（LN）、胶原含量变化及心肌超微结构的改变，探讨TGF－β1、细胞外基质（ECM）在糖尿病心肌病发病中的作用。方法 在电镜下观察心肌超微结构，用免疫组化方法测定心肌TGF－β1、FN、LN变化，用VG染色观察心肌胶原（Col)含量改变。结果 糖尿病大鼠较正常大鼠心肌组织中上述物质含量增加（P＜0．01）。电镜发现糖尿病心肌细胞肿胀，肌丝稀疏，线粒本肿胀、逸出，间质胶原增生及微血管基底膜增厚。结论 持续高血糖能导致心肌TGF－β1增加，使ECM在细胞间沉积，同时心肌细胞超微结构也发生改变，上述变化可能共同组成糖尿病心肌病的病理基础。     

转化生长因子-β1/Smdas信号转导通路与糖尿病心肌病变

转化生长因子-β1在糖尿病心肌病的发生发展过程中起着重要的调节作用,而Smads作为转化生长因子-β1受体胞内激活底物,除可介导转化生长因子-β1的信号转导外,还可介导非转化生长因子-β1途径的致心肌纤维化和心肌肥厚的信号转导.以转化生长因子-β1/Smads信号转导通路为治疗靶点,为防治糖尿病心肌病提供了新的思路.本文就这方面近来的研究进展作一综述.     

血小板反应素-1在前列腺癌中的表达及与血管生成的关系

目的 探讨各级前列腺癌组织中血小板反应素-1(TSP-1)的表达及与微血管密度(MVD)的关系.方法 采用免疫组织化学(SP)法检测30例前列腺增生组织及26例前列腺癌癌组织中TSP-1的表达情况及MVD.结果 前列腺增生组织及低分化前列腺癌癌组织中TSP-1表达强度及MVD计数分别为(3.7±1.5)、(1.7±1.0)及(6.8±1.9)、(31.0±5.3).TSP-1主要在前列腺增生组织基底细胞层高表达,在前列腺癌组织中低表达并且明显低于前列腺增生组织(P<0.01).MVD随着前列腺癌病变级别升高而增加,TSP-1的表达与MVD 呈显著负相关(rs=-0.603,P<0.01).结论 TSP-1 低表达可能参与了前列腺癌血管生成过程,联合检测TSP-1和MVD 可能在前列腺癌的早期筛查、诊断、治疗中具有一定意义.     

拮抗血管紧张素Ⅱ对5/6肾切除大鼠肾小管间质血小板反应蛋白1表达的影响

目的：观察血小板反应蛋白1（TSP1）在大鼠纤维化肾组织中的表达，以及血管紧张素Ⅱ（AngⅡ）对肾小管上皮细胞表达TSP1的影响。方法：建立5／6肾切除SD大鼠模型，设假手术组，手术组，氨氯地平组。缬沙坦组，雷米普利组。术后定时检测血压，分别于成模后0、4、12周取材，检测血肌酐、尿素氮、24h尿蛋白定量并计算Ccr。采用Masson染色观察肾小管间质纤维化（TIF）的程度；通过免疫组化观察TSP1、转化生长因子1（TGF-β1）、纤维连接蛋白（fibronectin，FN）在各组大鼠肾组织中表达及分布；采用免疫荧光共染技术观察TSP1／TGF-β1两者共区域表达随病变进展的变化；抽提肾皮质组织总RNA，RT—PCR法检测TSP1、TGF-β1和FN mRNA转录水平的表达。体外实验，以1 μM AngⅡ刺激人肾小管上皮细胞（HK-2）24h，10μM氯沙坦（Losartan）进行干预，分别采用RT-PCR、免疫荧光和Western blot检测TSP1、TGF-β1、FN mRNA转录水平和蛋白表达的改变，ELISA法检测培养基中活性和总TGF-β1的含量。结果：①正常大鼠肾小管间质基本无TSP1分布；而在5／6肾次全切大鼠的肾小管间质区内，小管上皮细胞、肌成纤维细胞和浸润的单核／巨噬细胞均能表达TSP1，12周手术组TSP1蛋白表达水平较假手术组上调近5倍：且较之0周和4周手术组亦明显增加（均P〈0．01），12周手术组TSP1mRNA和蛋白表达水平较假手术组分别上调1．94倍和5倍（均P〈0．05）；②TSP1表达增加与Ccr减退呈负相关（r=-0．472，P〈0．01）；12周手术组大鼠肾组织TIF程度以及TGF-β1、FN的表达较假手术组均明显上调（均P〈0．05），并与TSP1表达增加呈正相关；③缬沙坦／雷米普利处理组TSP1表达也上调，但程度明显低于手术组和氨氯地平组（均P〈0．05），而二组之间无差别；④AngⅡ能明显上调HK-2细胞TSP1、TGF—β1和FN mRNA转录水平和蛋白表达，而氯沙坦能抑制TSP1和TGF—β1的mRNA转录和蛋白合成，下调培养上清液中活性和总TGF-β1的含量。结论：肾小管间质病变的进展过程中，AngⅡ能使TSP1表达上调，其改变程度与肾功能损害密切相关；血管紧张素转换酶抑制剂／血管紧张素Ⅱ受体拮抗剂能减少TSPl和TGF—β1在纤维化肾组织中的表达，从而进一步对细胞外基质的沉积进行调节。     

褪黑素对糖尿病大鼠心肌转化生长因子-β1表达的影响

糖尿病(DM)心肌病是DM患者所特有的心脏病变，其病理特点是心肌细胞肥大、心肌纤维化和心肌微小血管广泛内膜病变。转化生长因子β1(TGF-β1)对细胞的生长、分化和免疫功能都有重要的调节作用。动物试验表明体内转染TGF-β1基因可促进心肌纤维化。Doi等用免疫组化方法证实，DM大鼠心脏TGF-β1表达显著增高。褪黑素(Me     

血小板反应蛋白-1 mRNA和微小RNA-194与2型糖尿病肾病的关系

目的 探讨血小板反应蛋白(TSP)-1 mRNA与微小RNA(miR)-194与2型糖尿病肾病的关系。方法 纳入2型糖尿病(T2DM)患者167例为T2DM组,随机选择健康体检者163例为健康对照组。再根据尿微量白蛋白/肌酐比值(UACR)将167例T2DM患者分为正常白蛋白尿组(UACR<30 mg/g, 56例)、微量白蛋白尿组(30 mg/g≤UACR<300 mg/g, 55例)及大量白蛋白尿组(UACR≥300 mg/g, 56例)。收集所有受试者的一般资料、实验室检查结果、miR-194及TSP-1 mRNA水平并分组进行比较。采用Pearson或Spearman相关分析探讨影响miR-194及TSP-1 mRNA表达水平的相关因素,采用多元线性逐步回归分析探讨影响miR-194及TSP-1 mRNA表达水平的独立因素。采用受试者工作特征(ROC)曲线探讨TSP-1 mRNA和miR-194对2型糖尿病肾病的诊断价值。结果 T2DM组患者收缩压、舒张压、空腹血浆葡萄糖(FPG)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白胆固醇(...     

血小板衍化生长因子-BB与糖尿病肾病

血小板衍化生长因子-BB(PDGF-BB)是PDGF经典的存在形式之一,其在肾脏中的作用主要包括诱导肾脏系膜细胞增生,促进细胞外基质积聚及单核-巨噬细胞在肾组织浸润。PDGF-BB在糖尿病肾病肾脏中表达增高,高水平的PDGF-BB可引起肾小球系膜细胞增生和细胞外基质积聚,亦参与肾小管及其间质改变,从而在糖尿病肾病的发生发展中起着重要作用。PDGF-BB还能通过诱导转化生长因子-β表达协同促进糖尿病肾病肾纤维化的发展。阻止PDGF-BB表达及其信号转导将有可能是糖尿病肾病的一种治疗手段。     

心肌营养素-1与糖尿病心肌病

心肌营养素-1(CT-1)是从小鼠胚胎干细胞中克隆出的一种细胞因子,为白细胞介素石细胞因子家族的新成员.CT-1可通过促进心肌细胞肥大、成纤维细胞的生长及胶原的合成,参与和调节心室肥厚及重构.糖尿病心肌病的病理生理过程中存在心肌重构,且2型糖尿病患者血浆中CT-1水平升高,表明CT-1可能在糖尿病心肌病的发生、发展中起重要的调节作用.确切的机制尚不清楚,可能与促进心肌重构有关.     

细胞因子和糖尿病心肌病

Diabetic cardiomyopathy (DCM), as an independent diabetic cardiac complication, has been paid more attention to. In clinical study, DCM was characterized by left ventricular diastolic dysfunction at the early stage. The pathogenesis of DCM is characterized by myocyte hypertrophy and cardiac fibrosis,ex-tracellular matrix accumulation and deposition. The development of DCM is multifactorial, the mechanism is still unclear. Several mechanisms are involved in the pathogenesis of DCM including myocardial fibrosis,in-terstitial inflammation and endothelial dysfunction. Cytokines can involve in multiple pathophysiological processes. In this review, the relationships between transforming growth factor-β1, connective tissue growth factor, tumor necrosis factor-α, insulin-like growth factor-1 ,adiponectin ,thrombospondin-1 and DCM are sum-marized. It may be the basis of therapeutic approaches for ameliorating DCM.     

细胞因子和糖尿病心肌病

Diabetic cardiomyopathy (DCM), as an independent diabetic cardiac complication, has been paid more attention to. In clinical study, DCM was characterized by left ventricular diastolic dysfunction at the early stage. The pathogenesis of DCM is characterized by myocyte hypertrophy and cardiac fibrosis,ex-tracellular matrix accumulation and deposition. The development of DCM is multifactorial, the mechanism is still unclear. Several mechanisms are involved in the pathogenesis of DCM including myocardial fibrosis,in-terstitial inflammation and endothelial dysfunction. Cytokines can involve in multiple pathophysiological processes. In this review, the relationships between transforming growth factor-β1, connective tissue growth factor, tumor necrosis factor-α, insulin-like growth factor-1 ,adiponectin ,thrombospondin-1 and DCM are sum-marized. It may be the basis of therapeutic approaches for ameliorating DCM.     

细胞因子和糖尿病心肌病

Diabetic cardiomyopathy (DCM), as an independent diabetic cardiac complication, has been paid more attention to. In clinical study, DCM was characterized by left ventricular diastolic dysfunction at the early stage. The pathogenesis of DCM is characterized by myocyte hypertrophy and cardiac fibrosis,ex-tracellular matrix accumulation and deposition. The development of DCM is multifactorial, the mechanism is still unclear. Several mechanisms are involved in the pathogenesis of DCM including myocardial fibrosis,in-terstitial inflammation and endothelial dysfunction. Cytokines can involve in multiple pathophysiological processes. In this review, the relationships between transforming growth factor-β1, connective tissue growth factor, tumor necrosis factor-α, insulin-like growth factor-1 ,adiponectin ,thrombospondin-1 and DCM are sum-marized. It may be the basis of therapeutic approaches for ameliorating DCM.     

细胞因子和糖尿病心肌病

Diabetic cardiomyopathy (DCM), as an independent diabetic cardiac complication, has been paid more attention to. In clinical study, DCM was characterized by left ventricular diastolic dysfunction at the early stage. The pathogenesis of DCM is characterized by myocyte hypertrophy and cardiac fibrosis,ex-tracellular matrix accumulation and deposition. The development of DCM is multifactorial, the mechanism is still unclear. Several mechanisms are involved in the pathogenesis of DCM including myocardial fibrosis,in-terstitial inflammation and endothelial dysfunction. Cytokines can involve in multiple pathophysiological processes. In this review, the relationships between transforming growth factor-β1, connective tissue growth factor, tumor necrosis factor-α, insulin-like growth factor-1 ,adiponectin ,thrombospondin-1 and DCM are sum-marized. It may be the basis of therapeutic approaches for ameliorating DCM.     

细胞因子和糖尿病心肌病

Diabetic cardiomyopathy (DCM), as an independent diabetic cardiac complication, has been paid more attention to. In clinical study, DCM was characterized by left ventricular diastolic dysfunction at the early stage. The pathogenesis of DCM is characterized by myocyte hypertrophy and cardiac fibrosis,ex-tracellular matrix accumulation and deposition. The development of DCM is multifactorial, the mechanism is still unclear. Several mechanisms are involved in the pathogenesis of DCM including myocardial fibrosis,in-terstitial inflammation and endothelial dysfunction. Cytokines can involve in multiple pathophysiological processes. In this review, the relationships between transforming growth factor-β1, connective tissue growth factor, tumor necrosis factor-α, insulin-like growth factor-1 ,adiponectin ,thrombospondin-1 and DCM are sum-marized. It may be the basis of therapeutic approaches for ameliorating DCM.     

细胞因子和糖尿病心肌病

Diabetic cardiomyopathy (DCM), as an independent diabetic cardiac complication, has been paid more attention to. In clinical study, DCM was characterized by left ventricular diastolic dysfunction at the early stage. The pathogenesis of DCM is characterized by myocyte hypertrophy and cardiac fibrosis,ex-tracellular matrix accumulation and deposition. The development of DCM is multifactorial, the mechanism is still unclear. Several mechanisms are involved in the pathogenesis of DCM including myocardial fibrosis,in-terstitial inflammation and endothelial dysfunction. Cytokines can involve in multiple pathophysiological processes. In this review, the relationships between transforming growth factor-β1, connective tissue growth factor, tumor necrosis factor-α, insulin-like growth factor-1 ,adiponectin ,thrombospondin-1 and DCM are sum-marized. It may be the basis of therapeutic approaches for ameliorating DCM.     

细胞因子和糖尿病心肌病

Diabetic cardiomyopathy (DCM), as an independent diabetic cardiac complication, has been paid more attention to. In clinical study, DCM was characterized by left ventricular diastolic dysfunction at the early stage. The pathogenesis of DCM is characterized by myocyte hypertrophy and cardiac fibrosis,ex-tracellular matrix accumulation and deposition. The development of DCM is multifactorial, the mechanism is still unclear. Several mechanisms are involved in the pathogenesis of DCM including myocardial fibrosis,in-terstitial inflammation and endothelial dysfunction. Cytokines can involve in multiple pathophysiological processes. In this review, the relationships between transforming growth factor-β1, connective tissue growth factor, tumor necrosis factor-α, insulin-like growth factor-1 ,adiponectin ,thrombospondin-1 and DCM are sum-marized. It may be the basis of therapeutic approaches for ameliorating DCM.     

细胞因子和糖尿病心肌病

Diabetic cardiomyopathy (DCM), as an independent diabetic cardiac complication, has been paid more attention to. In clinical study, DCM was characterized by left ventricular diastolic dysfunction at the early stage. The pathogenesis of DCM is characterized by myocyte hypertrophy and cardiac fibrosis,ex-tracellular matrix accumulation and deposition. The development of DCM is multifactorial, the mechanism is still unclear. Several mechanisms are involved in the pathogenesis of DCM including myocardial fibrosis,in-terstitial inflammation and endothelial dysfunction. Cytokines can involve in multiple pathophysiological processes. In this review, the relationships between transforming growth factor-β1, connective tissue growth factor, tumor necrosis factor-α, insulin-like growth factor-1 ,adiponectin ,thrombospondin-1 and DCM are sum-marized. It may be the basis of therapeutic approaches for ameliorating DCM.     

细胞因子和糖尿病心肌病

Diabetic cardiomyopathy (DCM), as an independent diabetic cardiac complication, has been paid more attention to. In clinical study, DCM was characterized by left ventricular diastolic dysfunction at the early stage. The pathogenesis of DCM is characterized by myocyte hypertrophy and cardiac fibrosis,ex-tracellular matrix accumulation and deposition. The development of DCM is multifactorial, the mechanism is still unclear. Several mechanisms are involved in the pathogenesis of DCM including myocardial fibrosis,in-terstitial inflammation and endothelial dysfunction. Cytokines can involve in multiple pathophysiological processes. In this review, the relationships between transforming growth factor-β1, connective tissue growth factor, tumor necrosis factor-α, insulin-like growth factor-1 ,adiponectin ,thrombospondin-1 and DCM are sum-marized. It may be the basis of therapeutic approaches for ameliorating DCM.     

细胞因子和糖尿病心肌病

Diabetic cardiomyopathy (DCM), as an independent diabetic cardiac complication, has been paid more attention to. In clinical study, DCM was characterized by left ventricular diastolic dysfunction at the early stage. The pathogenesis of DCM is characterized by myocyte hypertrophy and cardiac fibrosis,ex-tracellular matrix accumulation and deposition. The development of DCM is multifactorial, the mechanism is still unclear. Several mechanisms are involved in the pathogenesis of DCM including myocardial fibrosis,in-terstitial inflammation and endothelial dysfunction. Cytokines can involve in multiple pathophysiological processes. In this review, the relationships between transforming growth factor-β1, connective tissue growth factor, tumor necrosis factor-α, insulin-like growth factor-1 ,adiponectin ,thrombospondin-1 and DCM are sum-marized. It may be the basis of therapeutic approaches for ameliorating DCM.     

促血管生成素-1对糖尿病大鼠肾脏色素上皮衍生因子和血小板反应蛋白-1基因表达的影响

目的 观察色素上皮衍生因子（PEDF）、血小板反应蛋白-1（TSP-1）在糖尿病大鼠肾脏的表达变化,探讨促血管生成素-1（Ang-1）对上述因子的影响. 方法 将雄性SD大鼠分正常对照（NC）组、DN组、空载处理（BV）组、Ang-1处理（AV）组.采用STZ腹腔注射诱导大鼠DN模型.成模8周后尾静脉注射Ang-1腺病毒载体.多时点检测24 hUAlb和肾组织PEDF、TSP-1蛋白及mRNA表达水平.结果 DN、BV、AV组24 hUAlb均升高,其中AV组于20周后降低（P＜0.05）.DN、BV、AV组肾组织PEDF蛋白及mRNA表达下调,TSP-1表达上调（P＜0.05）,其中AV组12周后肾组织PEDF和TSP-1mRNA及蛋白表达变化较DN、BV组改善明显（P＜0.05）. 结论 糖尿病大鼠肾脏PEDF、TSP-1异常表达参与DN发生发展,给予Ang-1可改善糖尿病大鼠肾脏PEDF、TSP-1异常表达.