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纤溶酶激活物抑制物1和三磷酸腺苷结合盒转运体B1(C3435T)基因多态性对使用糖皮质激素药物患者股骨头坏死的诊断价值
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作者 刘小玲 梁金冰 +1 位作者 蒋粤桂 黄艳萍 《中外医药研究》 2023年第31期145-147,共3页
目的:分析纤溶酶激活物抑制物1(PAI-1)和三磷酸腺苷结合盒转运体B1(ABCB1)(C3435T)基因多态性对使用糖皮质激素药物患者股骨头坏死(ONFH)的诊断价值。方法:选取2019年9月—2022年1月于茂名市人民医院使用糖皮质激素药物治疗的系统性红... 目的:分析纤溶酶激活物抑制物1(PAI-1)和三磷酸腺苷结合盒转运体B1(ABCB1)(C3435T)基因多态性对使用糖皮质激素药物患者股骨头坏死(ONFH)的诊断价值。方法:选取2019年9月—2022年1月于茂名市人民医院使用糖皮质激素药物治疗的系统性红斑狼疮(SLE)患者61例作为研究对象,将继发ONFH的30例患者作为ONFH组,将同期行基因检测且未发生ONFH的31例患者作为非ONFH组。检测两组患者的PAI-1(4G/5G)和ABCB1(C3435T)的基因多态性。结果:非ONFH组和ONFH组患者的性别、年龄、身体质量指数、受教育程度、居住地、激素起始量、激素使用累积量>10 g、激素冲击以及合并LN等情况比较,差异无统计学意义(P>0.05)。ONFH组PAI-1中4G4G型患者占比高于非ONFH组,5G4G型/5G5G型占比低于非ONFH组,差异有统计学意义(P=0.024);ONFH组ABCB1(C3435T)中CC型患者占比高于非ONFH组,CT型/TT型患者占比低于非ONFH组,差异有统计学意义(P=0.028)。结论:PAI-1和ABCB1(C3435T)分型与使用糖皮质激素药物治疗的SLE患者发生ONFH密切相关。 展开更多
关键词 系统性红斑狼疮 激活抑制1 三磷酸腺苷结合盒转运体B1 基因多态性 股骨头坏死
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纤溶酶原激活物抑制物-1与胰岛素抵抗及冠心病 被引量:1
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作者 胡淑国 《实用心脑肺血管病杂志》 2001年第1期59-61,共3页
纤溶酶原激活物抑制物 - 1(PAI- 1)是重要的生理性纤溶酶原激活物 (PA)的抑制物 ,过多的 PAI- 1导致血浆中 PA活性下降 ,容易形成血栓。PAI- 1与胰岛素抵抗 (IR)综合征及其相关的肥胖和动脉粥样硬化等有关 ,这种关系可以解释 IR病人发... 纤溶酶原激活物抑制物 - 1(PAI- 1)是重要的生理性纤溶酶原激活物 (PA)的抑制物 ,过多的 PAI- 1导致血浆中 PA活性下降 ,容易形成血栓。PAI- 1与胰岛素抵抗 (IR)综合征及其相关的肥胖和动脉粥样硬化等有关 ,这种关系可以解释 IR病人发生冠状动脉粥样硬化性心脏病的危险性大为增加。 展开更多
关键词 激活抑制-1 胰岛素抵抗 冠心病
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急性心肌梗死与纤溶酶原激活抑制物-1及其基因多态性相关性研究 被引量:2
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作者 蒋建中 尹士全 孙根义 《吉林医学》 CAS 2010年第27期4684-4685,共2页
目的:从基因水平揭示AMI发病的危险因素。纤溶酶原激活剂抑制物-1(PAI-1)活性及其等位基因多态性与急性心肌梗死(AMI)之间的关系。方法:AMI组:55例;对照组:48例健康者。分别应用特异性寡核苷酸点膜杂交技术,PAI-1启动子区4G/5G多态性分... 目的:从基因水平揭示AMI发病的危险因素。纤溶酶原激活剂抑制物-1(PAI-1)活性及其等位基因多态性与急性心肌梗死(AMI)之间的关系。方法:AMI组:55例;对照组:48例健康者。分别应用特异性寡核苷酸点膜杂交技术,PAI-1启动子区4G/5G多态性分析,测定血浆PIA-1活性(用发色底物法)。结果:AMI组和对照组中4G/5G基因型的血浆PAI-1活性水平最高,与4G/5G基因型,5G/5G基因型比较差异有统计学意义(P<0.05)。结论:血浆PAI-1活性增高是AMI发病的危险因素之一,4G/4G纯合子基因型是AMI发病的危险基因型。 展开更多
关键词 急性心肌梗死 激活抑制-1 基因多态性
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中西医结合治疗脑梗死急性期对组织型纤溶酶原激活物及其抑制物的影响 被引量:5
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作者 张汉明 《实用中医药杂志》 2017年第8期923-924,共2页
目的:观察中西医结合治疗脑梗死急性期对组织型纤溶酶原激活物(t-PA)及其抑制物(PAI)的影响。方法:82例随机分为对照组和观察组各41例。两组均用常规西药治疗,观察组加用化痰祛瘀汤。结果:观察组NIHSS评分、BI指数评分均显著优于对照组(... 目的:观察中西医结合治疗脑梗死急性期对组织型纤溶酶原激活物(t-PA)及其抑制物(PAI)的影响。方法:82例随机分为对照组和观察组各41例。两组均用常规西药治疗,观察组加用化痰祛瘀汤。结果:观察组NIHSS评分、BI指数评分均显著优于对照组(P<0.05),治疗后观察组t-PA和PAI指标均显著优于对照组(P<0.05)。结论:中西医结合治疗脑梗死急性期效果更好,可显著改善神经损伤程度,提高生活能力,促使t-PA水平升高及PAI水平降低。 展开更多
关键词 脑梗死急性期 中西医结合治疗 组织型激活 组织型激活抑制
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激素性股骨头坏死与纤溶功能及血液流变性的实验研究 被引量:4
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作者 胡波 尹良军 +1 位作者 陈伟 方利 《微循环学杂志》 2002年第4期40-41,共2页
目的 :探讨纤溶功能紊乱和血液高粘滞性在激素性股骨头坏死中的作用。方法 :在家兔皮下注射地塞米松 (实验 1组 )、地塞米松加血速宁 (实验 2组 )后 ,动态观察 15日、3 0日、60日t PA和PAI、t PA/PAI、全血粘度和血浆粘度的变化。结果 ... 目的 :探讨纤溶功能紊乱和血液高粘滞性在激素性股骨头坏死中的作用。方法 :在家兔皮下注射地塞米松 (实验 1组 )、地塞米松加血速宁 (实验 2组 )后 ,动态观察 15日、3 0日、60日t PA和PAI、t PA/PAI、全血粘度和血浆粘度的变化。结果 :实验 1组t PA/API比值在实验 15日与对照组无显著差异 (P >0 .0 5) ,在实验 3 0日下降至 1/8,在 60日t PA/PAI比值有所增加 ,但仍显著低于对照组 (P <0 .0 1) ;实验 2组在实验第 15日 ,t PA/PAI比值显著低于实验 1组 (P <0 .0 1) ,在实验第 3 0日与实验 1组无显著差异 (P >0 .0 5) ;血液高切粘度、低切粘度、血浆粘度在实验第 15日均高于对照组 (P <0 .0 1) ,以后逐渐下降 ,在 60日各指标与对照组无显著差异 (P >0 .0 5)。结论 :股骨头缺血坏死可能与血液纤溶功能紊乱。 展开更多
关键词 纤溶酶激活抑制物 激活 激素性股骨头坏死 功能 血液流变性 实验研究
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丹参对糖尿病大鼠肾脏的保护作用及其机制研究 被引量:51
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作者 柳刚 关广聚 +5 位作者 亓同钢 傅余芹 李学刚 孙云 吴涛 文蓉珠 《中西医结合学报》 CAS 2005年第6期459-462,共4页
目的:探讨丹参对糖尿病大鼠肾脏的保护作用及其机制。方法:采用单侧肾切除、腹腔注射链脲佐菌素诱导糖尿病肾病大鼠模型,予以丹参药物干预。观察大鼠肾脏形态学及肾功能的变化。采用荧光实时定量逆转录-聚合酶链反应法检测转化生长因子... 目的:探讨丹参对糖尿病大鼠肾脏的保护作用及其机制。方法:采用单侧肾切除、腹腔注射链脲佐菌素诱导糖尿病肾病大鼠模型,予以丹参药物干预。观察大鼠肾脏形态学及肾功能的变化。采用荧光实时定量逆转录-聚合酶链反应法检测转化生长因子β1(transforming growth factor-beta1,TGF-β1)、结缔组织生长因子(connective tissue growth factor,CTGF)、纤溶酶原激活物抑制物1(plasminogen activator inhibi-tor-1,PAI-1)等细胞因子在糖尿病大鼠肾皮质中的表达水平。结果:与正常对照组比较,用药第8周末糖尿病肾病模型组大鼠的肾脏肥大指数、平均肾小球体积、尿白蛋白排泄率、肌酐清除率均有明显升高(P<0.05),肾皮质TGF-β1、CTGF、PAI-1和纤维连接蛋白的表达水平也有显著增高(P<0.05)。丹参治疗组大鼠的上述指标与糖尿病肾病模型组比较,则有明显的降低(P<0.05)。结论:丹参可通过抑制TGF-β1、CTGF、PAI-1等细胞因子的表达,从而对糖尿病大鼠肾脏起保护作用。 展开更多
关键词 链脲霉素糖尿病 丹参 转化生长因子Β1 结缔组织生长因子 激活抑制1
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An Experimental Study of Pathogenesis of Steroid-induced Avascular Necrosis of Femoral Head 被引量:1
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作者 李毅 陈君长 +3 位作者 康斌 王坤正 张珍妮 同志超 《Journal of Nanjing Medical University》 2003年第4期191-195,共5页
Objective: To explore the pathogenesis of avascular necrosis of femoral head(ANFH) and search an effective method for clinical practice. Methods: Twenty-four Japanese rabbitswere divided into 2 groups of models and co... Objective: To explore the pathogenesis of avascular necrosis of femoral head(ANFH) and search an effective method for clinical practice. Methods: Twenty-four Japanese rabbitswere divided into 2 groups of models and controls. ANFH models were produced byintramuscular-injection of large dosage of steroid to rabbits for 8 weeks. From the 4th, 8th and12th week after production of models, 2 rabbits of each group were sacrificed to observe thestructure of femoral head through light microscope and scanning electron microscope. The contents ofNitric Oxide (NO), tissue-type plasminogen activator (t-PA) and -plasminogen activator inhibitor(PAI) in plasma of the 4 rabbits in each group were estimated at the same time. Results: Comparedwith control group, the rabbits of model group exhibited many differences: such as osteoporosis offemoral head, the presence of more bone lacuna and fat cell through light microscope observing; thebroken and sunk bone trabecula, the loosen and broken collagen fibers on the surface of bone matrixthrough scanning electron microscope observing. Compared with control group, the Concentration ofNO and t-PA in plasma of the model rabbits decreased obviously, but the Concentration of the PAIincreased obviously. Conclusion: The steroid-induced ANFH might be related to the lower level of NOand the descent of fibrinolytic activity. 展开更多
关键词 femoral head necrosis pathological process nitric oxide tissue-typeplasminogen activator plasminogen activator inhibitor
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t-PA,PAI-1在脑梗死、脑出血病患者中的检测及临床意义 被引量:1
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作者 丁元深 葛梅 +1 位作者 刘贤忠 牟青杰 《潍坊医学院学报》 2007年第4期301-303,共3页
目的研究纤溶指标组织型纤溶酶原激活物(t-PA)、纤溶酶激活物抑制物-1(PAI-1)抗原含量在脑梗死(C I)、脑出血(CH)患者血浆中治疗前后的变化及其临床意义。方法用酶联免疫吸附双抗体夹心法(ELISA)分别检测30例C I、20例CH患者血浆t-PA PA... 目的研究纤溶指标组织型纤溶酶原激活物(t-PA)、纤溶酶激活物抑制物-1(PAI-1)抗原含量在脑梗死(C I)、脑出血(CH)患者血浆中治疗前后的变化及其临床意义。方法用酶联免疫吸附双抗体夹心法(ELISA)分别检测30例C I、20例CH患者血浆t-PA PAI-1的抗原含量水平治疗前后的含量变化。结果①与对照组比较:C I患者组t-PA、PAI-1抗原含量水平均高于对照组(P<0.05);CH组t-PA高于对照组(P<0.05),PAI-1低于对照组(P<0.05)。②治疗后的比较:血浆t-PA水平在C I和CH两组治疗前、后的变化均无统计学意义(P>0.05);血浆PAI-1抗原含量在C I组患者治疗后明显低于治疗前(P<0.05),而在CH组患者治疗后是增高的(P<0.05),治疗后两组的PAI-1抗原含量水平均与对照组无差异。结论t-PA抗原含量水平在脑梗死组、脑出血组患者均升高。PAI-1抗原含量水平在脑梗死组患者升高,在脑出血组降低,可作为判断病情严重程度、预后与复发及判断病程、病期的参考指标。 展开更多
关键词 血浆组织型激活 激活抑制-1 脑出血 脑梗死
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INVESTIGATION OF THROMBOMODULIN AND PLASMINOGEN ACTIVATOR INHIBITOR TYPE-I IN PREGNANCY INDUCED HYPERTENSION AND ITS CLINICAL SIGNIFICANCE 被引量:6
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作者 马水清 白春梅 边旭明 《Chinese Medical Sciences Journal》 CAS CSCD 2001年第3期169-171,共3页
Objective. To measure the circulating levels of thrombomodulin (TM) and plasminogen activator inhibitor type- I (PAI- I) in women with pregnancy induced hypertension (PIH). Methods. Blood samples were drawn from 97 pr... Objective. To measure the circulating levels of thrombomodulin (TM) and plasminogen activator inhibitor type- I (PAI- I) in women with pregnancy induced hypertension (PIH). Methods. Blood samples were drawn from 97 pregnant women in their third trimester, grouped as 25 mild PIH,26 moderate PIH,22 severe PIH and 24 normotensive healthy pregnant women for determining levels of TM by ELISA,PAI- I by colorimetric assay methods, and creatinine (Cr) in serum by biochemical method. Results. Circulating levels of TM, PAI- I and TM/Cr ratio increased with increasing severity of PIH. There were no significant differences between mild and normotensive pregnant women. The parameters were significantly changed in the moderate and severe PIH groups. Conclusion. TM and PAI- I may serve as meaningful clinical markers for the assessment of the endothelial damage in PIH, which is very important in evaluating and following the development of PIH. 展开更多
关键词 pregnancy complication HYPERTENSION plasminogen activator inhibitor THROMBOMODULIN
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不同程度甲状腺机能减退症患者纤溶活性的检测及临床意义 被引量:1
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作者 栾炳国 王德文 +1 位作者 栾丽娟 逄力男 《社区医学杂志》 2009年第15期36-37,共2页
目的研究D-二聚体(DDM)、组织型纤溶酶原激活物(t-PA)、纤溶酶激活物抑制物-1(PA-1)在不同程度甲状腺机能减退症(甲减)患者中的检测及其临床意义。方法根据促甲状腺激素(TSH)水平选取不同程度甲减患者及健康人(对照组)检测DDM、t-PA、PA... 目的研究D-二聚体(DDM)、组织型纤溶酶原激活物(t-PA)、纤溶酶激活物抑制物-1(PA-1)在不同程度甲状腺机能减退症(甲减)患者中的检测及其临床意义。方法根据促甲状腺激素(TSH)水平选取不同程度甲减患者及健康人(对照组)检测DDM、t-PA、PAI-1血浆含量。数据采用SPSS11.5for windows软件进行统计分析。结果与对照组比较,轻度甲减的DDM水平降低(P<0.05),而t-PA、PAI-1水平增高(P<0.01)。与之相反,重度甲减患者其DDM水平升高(P<0.01),而t-PA、PAI-1水平降低(P<0.05)。结论不同程度的甲状腺功能减低对血液纤溶活性的影响不同,轻度甲减患者血液纤溶活性降低,呈高凝状态,容易出现血栓形成;重度甲减患者血液纤溶活性增强,存在出血倾向。 展开更多
关键词 甲状腺机能减退症 D-二聚体 组织型激活 激活抑制-1
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High level of urokinase plasminogen activator contributes to cholangiocarcinoma invasion and metastasis 被引量:5
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作者 Parichut Thummarati Sitsom Wijitburaphat +4 位作者 Aruna Prasopthum Apaporn Menakongka Banchob Sripa Rutaiwan Tohtong Tuangporn Suthiphongchai 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第3期244-250,共7页
AIM: To investigate the role of urokinase plasminogen activator (uPA) in cholangiocarcinoma (CCA) invasion and its correlation with clinicopathological parameters. METHODS: uPA expression in CCA tissue was determined ... AIM: To investigate the role of urokinase plasminogen activator (uPA) in cholangiocarcinoma (CCA) invasion and its correlation with clinicopathological parameters. METHODS: uPA expression in CCA tissue was determined by immunohistochemistry. The level of uPA from two CCA cell lines (HuCCA-1 and KKU-M213) and a noncancer immortalized cholangiocyte cell line (H69) was monitored by plasminogen-gelatin zymography and western blotting, whereas that of plasminogen activator inhibitor type 1 (PAI-1) protein and uPA receptor (uPAR)mRNA was monitored by western blotting and quantitative real-time reverse transcriptase polymerase chain reaction, respectively. Two independent methods were employed to suppress uPA function: a synthetic uPA inhibitor (B428) and silencing of uPA gene expression using siRNA. In vitro invasion of the uPA-disrupted cells was assessed by Matrigel-coated Transwell assay. RESULTS: The immunohistochemical study showed that 75.3% (131/174) of CCA tissues expressed uPA. High uPA expression was correlated with lymphatic invasion and metastasis of CCA patients. Plasminogen-gelatin zymography of the conditioned media and cell-surface eluates showed that both CCA cell lines, but not H69, expressed both secreted and membrane-bound forms of uPA. Although the two CCA cell lines, HuCCA-1 and KKU-M213, expressed a relatively high level of uPA and uPAR, the latter exhibited a much lower degree of in vitro invasiveness, correlating with a high expression of PAI-1 in the latter, but not in the former. Suppressing uPA function with a specific uPA inhibitor, B428, or with siRNA against uPA reduced in vitro invasiveness of KKU-M213 cells, demonstrating the requirement for uPA in the invasiveness of CCA cells. Therefore, our in vivo and in vitro studies suggest that uPA is an important requirement for the invasion process of CCA. CONCLUSION: uPA expression correlates with lymphatic invasion and metastasis in vivo and is required for CCA cell invasion in vitro , suggesting its potential as a therapeutic target. 展开更多
关键词 Bile duct cancer Cholangiocarcinoma Cancer invasion Urokinase plasminogen activator Cancer metastasis
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老年冠心病患者血浆PAI-1及C-反应蛋白浓度的变化
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作者 杨月榕 罗助荣 《心血管康复医学杂志》 CAS 2001年第6期522-523,共2页
目的 :探讨血浆纤溶酶原激活物抑制物 - 1(PAI- 1)及血浆 C-反应蛋白 (C- RP)与不稳定型心绞痛的关系。方法 :对比观察 2 1例老年不稳定型心绞痛 (UAP)患者与 19例老年稳定型心绞痛 (SAP)患者及 2 0例健康对照者例的血浆 PAI- 1及 C- R... 目的 :探讨血浆纤溶酶原激活物抑制物 - 1(PAI- 1)及血浆 C-反应蛋白 (C- RP)与不稳定型心绞痛的关系。方法 :对比观察 2 1例老年不稳定型心绞痛 (UAP)患者与 19例老年稳定型心绞痛 (SAP)患者及 2 0例健康对照者例的血浆 PAI- 1及 C- RP浓度的变化。结果 :2 1例 U AP患者的 PAI- 1及 C- RP浓度显著高于 SAP组患者及对照组的(P<0 .0 1)。结论 :血浆 PAI- 1及 C- RP浓度变化在不稳定型心绞痛的发生及发展过程中有重要作用。 展开更多
关键词 心绞痛 血浆激活抑制 C-反应蛋白 UAP
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Expression of Plasminogen Activator Inhibitor-2 is Negatively Associated with Invasive Potential in Hepatocellular Carcinoma Cells
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作者 Ye Jin Li Zhou +1 位作者 Ke-min Jin Bao-cai Xing 《Chinese Medical Sciences Journal》 CAS CSCD 2013年第1期16-19,共4页
Objective To investigate the association between plasminogen activator inhibitor(PAI)-2 expression and invasive potential in hepatocellular carcinoma(HCC) cells.Methods The HCC cell lines with high,low,and non-metasta... Objective To investigate the association between plasminogen activator inhibitor(PAI)-2 expression and invasive potential in hepatocellular carcinoma(HCC) cells.Methods The HCC cell lines with high,low,and non-metastatic potentials,namely MHCC97-H,MHCC97-L,and SMMC-7721 respectively,were cultured in vitro.Matrigel invasion assay and Western blot of PAI-2 protein expression were conducted.Results The number of invaded cells in MHCC97-L was significantly higher than that in SMMC-7721(P=0.005),whereas that in MHCC97-H was higher than in MHCC97-L(P=0.017) and SMMC-7721(P=0.001).Contrarily,PAI-2 protein expression was gradually reducing from SMMC-7721,MHCC97-L,to MHCC97-H(MHCC97-H vs.MHCC97-L,P<0.001;MHCC97-H vs.SMMC-7721,P=0.001;MHCC97-L vs.SMMC-7721,P=0.001).The Pearson's correlation analysis revealed a significant negative association between invaded cell number and PAI-2 expression(r= 0.892,P=0.001).Conclusion PAI-2 expression may be negatively associated with the invasive potential of HCC. 展开更多
关键词 hepatocellular carcinoma plasminogen activator inhibitor-2 invasive potential
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Tissue-type plasminogen activator and plasminogen activator inhibitor type-1 mRNA and their protein expression levels in human decidua after early pregnancy termination by mifepristone plus misoprostol
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作者 黄丽丽 石一复 《Chinese Medical Journal》 SCIE CAS CSCD 2001年第6期68-71,108,共5页
Objective To investigate the mechanism of prolonged uterine hemorrhage after terminating early pregnancy by mifepristone plus misoprostol.Methods Forty-five decidua specimens were obtained from 45 pregnant women wit... Objective To investigate the mechanism of prolonged uterine hemorrhage after terminating early pregnancy by mifepristone plus misoprostol.Methods Forty-five decidua specimens were obtained from 45 pregnant women with amenorrhea of 6-7 week duration. Fifteen women were treated with mifepristone and 15 were treated with mifepristone plus misoprostol. The remaining 15 served as controls. The tPA and PAI-1 mRNA levels were estimated by reverse transcription-polymerase chain reaction. Chromogenic assay and enzyme-linked immunosorbent assay were used to detect tPA activity and PAI-1 protein level in decidua. Results The activities of tPA in the mifepristone plus misoprostol group and in the mifepristone group were 46.91±20.74?IU/mg*protein and 64.25±35.81?IU/mg*protein respectively, lower than those in the normal decidua group (99.76±58.61?IU/mg*protein, P<0.05). tPA mRNA levels in the mifepristone plus misoprostol group were the highest (1.43±0.39) among the groups. In the mifepristone group, tPA mRNA level (0.90±0.16) was not significantly different from that in the normal decidua group (0.94±0.17). The protein and mRNA expression levels of PAI-1 were not significantly different among the three groups (P>0.05).Conclusions Mifepristone plus misoprostol decreased tPA activity in human early decidua by post-transcription pathways, which may influence decidua shedding, endometrial angiogenesis, endometrial remodeling, and cause prolonged uterine hemorrhage after drug abortion. 展开更多
关键词 tissue-type plasminogen activator · plasminogen activator inhibitor type-1 · mifepristone · decidua · uterine hemorrhage
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Endothelium-specific SIRT1 overexpression inhibits hyperglycemia-induced upregulation of vascular cell senescence 被引量:16
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作者 CHEN HouZao WAN YanZhen +9 位作者 ZHOU Shuang LU YunBiao ZHANG ZhuQin ZHANG Ran CHEN Feng HAO DeLong ZHAO Xiang GUO ZhiChen LIU DePei LIANG ChihChuan 《Science China(Life Sciences)》 SCIE CAS 2012年第6期467-473,共7页
The rapidly increasing prevalence of diabetes mellitus worldwide is one of the most serious and challenging health problems in the 21st century. Mammalian sirtuin 1 (SIRT1) has been shown to decrease high-glucose-in... The rapidly increasing prevalence of diabetes mellitus worldwide is one of the most serious and challenging health problems in the 21st century. Mammalian sirtuin 1 (SIRT1) has been shown to decrease high-glucose-induced endothelial cell senescence in vitro and prevent hyperglycemia-induced vascular dysfunction. However, a role for SIRTI in prevention of hyperglyce- mia-induced vascular cell senescence in vivo remains unclear. We used endothelium-specific SIRT1 transgenic (SIRT1-Tg) mice and wild-type (WT) mice to construct a 40-week streptozotocin (STZ)-induced diabetic mouse model. In this mode, 42.9% of wild-type (WT) mice and 38.5% of SIRT1-Tg mice were successfully established as diabetic. Forty weeks of hyper- glycemia induced significant vascular cell senescence in aortas of mice, as indicated by upregulation of expression of senes- cence-associated markers including p53, p21 and plasminogen activator inhibitor-1 (PAI-1). However, SIRT1-Tg diabetic mice displayed dramatically decreased expression of p53, p21 and PAI-I compared with diabetic WT mice. Moreover, man- ganese superoxide dismutase expression (MnSOD) was significantly downregulated in the aortas of diabetic WT mice, but was preserved in diabetic SIRT1-Tg mice. Furthermore, expression of the oxidative stress adaptor p66Shc was significantly de- creased in aortas of SIRT1-Tg diabetic mice compared with WT diabetic mice. Overall, these findings suggest that SIRT 1-mediated inhibition of hyperglycemia-induced vascular cell senescence is mediated at least partly through the reduction of oxidative stress. 展开更多
关键词 SIRT1 HYPERGLYCEMIA vascular cell senescence
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Assessment of ghrelin and leptin receptor levels in postmenopausal women who received oral or transdermal menopausal hormonal therapy
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作者 Barbara RUSZKOWSKA Alina SOKUP +4 位作者 Arleta KULWAS Maciej W.SOCHA Krzysztof GóRALCZYK Barbara GóRALCZYK Danuta ROS 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2012年第1期35-42,共8页
Objective: In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghreli... Objective: In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghrelin, total ghrelin, leptin receptor, lipoprotein(a) (Lp(a)), and plasminogen activator inhibitor type 1 (PAl-l) in postmenopausal women who received oral or transdermal menopausal hormonal therapy (MHT). Methods: The study involved 76 healthy women: 46 women aged from 44 to 58 years who received oral (26) or transdermal (20) MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT. The plasma concentrations of total ghrelin, the active form of ghrelin, Lp(a), and PAI-I:Ag were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of the leptin receptor was measured by enzyme immunometric assay (EIA). Results: We observed a significantly higher concentration o~ total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT. We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group. A higher concentration of PAl-1 :Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group. The differences were statistically significant. Additionally, we found a significant negative correlation between the concentrations of total ghrelin and PAl-1 :Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT. Conclusions: The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT. This indicates a beneficial effect of the transdermal route of MHT. However, transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAl-1 :Ag, which in turn, can lead to a reduction in fibrinolytic activity. 展开更多
关键词 Menopausal hormonal therapy (MHT) Plasminogen activator inhibitor type 1 (PAl-l) Leptin receptor GHRELIN MENOPAUSE
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