血管紧张素类

摘要： 目的研究血管紧张素(Ang)家族新成员Ang-(1-9)对动脉粥样硬化中关键黏附分子血管细胞黏附分子1(VCAM-1)表达的作用及调控机制。方法在体外培养人脐静脉内皮细胞,给予相应刺激进行分组:对照组;AngⅡ为实验1组;Ang-(1-9)为实验2组;AngⅡ+Ang-(1-9)为实验3组;AngⅡ+氯沙坦为实验4组;AngⅡ+Ang-(1-9)+PD123319为实验5组。采用RT-PCR及流式细胞仪检测VCAM-1 mRNA及蛋白表达,荧光素酶报告基因检测法测定VCAM-1启动子活性,酶联免疫吸附法测定NF-κB细胞核内水平,细胞免疫荧光观察NF-κB细胞核内转移情况。结果与对照组比较,实验1组VCAM-1 mRNA和蛋白表达明显增加(2.61±0.05 vs 1.00±0.00,146.35±1.81 vs 11.17±0.52,P<0.05);与实验1组比较,实验3组和实验4组VCAM-1 mRNA和蛋白表达明显减少,差异有统计学意义(P<0.05)。与对照组比较,实验1组VCAM-1启动子活性和NF-κB在细胞核内表达明显增加,差异有统计学意义(P<0.05);与实验1组比较,实验3组VCAM-1启动子活性和NF-κB在细胞核内表达明显降低,差异有统计学意义(P<0.05);与实验3组比较,实验5组VCAM-1启动子活性和NF-κB在细胞核内表达明显增加,差异有统计学意义(P<0.05)。结论Ang-(1-9)对VCAM-1的抑制作用有助于为动脉粥样硬化疾病的防治提供新思路。

摘要： 目的观察急性白血病(AL)细胞表面肾素血管紧张素系统(RAS)中关键因子血管紧张素Ⅱ受体1(AT1R)的表达情况,观察各类AL中RAS系统关键因子的不同表达及其与疾病增殖复发、浸润转移的相关性。方法选取内蒙古科技大学包头医学院第一附属医院血液内科2017年1月至2019年12月收治的AL初治患者60例为病例组(分为AML组30例,ALL组30例),缺铁性贫血患者60例为对照组,采用流式细胞仪检测AL细胞表面RAS系统中关键因子AT1R的表达情况。结果病例组患者骨髓原始细胞表面AT1R的表达阳性率高于对照组(P<0.05),且AML组AT1R表达阳性率高于ALL组(P<0.05)。化疗1周期后,达完全缓解患者骨髓原始细胞表面AT1R的表达阳性率低于未达缓解患者(P<0.05)。结论AL细胞表面AT1R表达水平增高。不同类型AL表达水平不同,初发AML中表达更加明显,完全缓解后AL中AT1R的表达低于未缓解组水平,其可能通过促进肿瘤血管新生参与疾病增殖复发,AT1R可能是AL联合治疗的一个潜在靶点。

摘要： Objective To investigate the effects of agonist of angiotensin-(1-7)(AVE0991) on endothelial function and atherogenesis in apolipoprotein E knockout (ApoE-/-) mice.Methods Eight-week-old ApoE-/-male mice and C57BL/6J male mice were randomly divided into 3 groups:a normal diet control group(ND,n=10),a high-fat diet group(HFD,n=10),and a high-fat diet with AVE0991 0.58 μmol · kg-1 · d-1 group(HFD+ AVE0991,n=10).After 12 weeks of treatment,serum levels of lipids and parameters of endothelial function were measured.Atherosclerotic lesions in aorta roots were detected by Oil Red O staining.CD31 levels in the arterial intima were analyzed by immunohistochemistry.Results AVE0991 had no effects on blood lipids (P ＞ 0.05)but lowered serum levels of nitric oxide in high-fat diet mice(76.8±34.4 μmol/L vs.116.8±33.9 μmol/L,P＜0.05).Also,AVE0991 had no effects on the activity of serum nitric oxide synthase(19.5±5.7 U/ml vs.17.9±3.3 U/ml,P＞0.05)but decreased the activity of serum induced nitric oxide synthase(9.0 ±2.3 U/ml vs.12.7 ± 3.2 U/ml,P ＜0.05) and increased the ratio of phosphorylated endothelial nitric oxide synthase to induced nitric oxide synthase in the vessel wall in high-fat diet mice(0.8±0.2％ vs.0.6 ± 0.2％,P ＜ 0.05).AVE0991 decreased serum levels of C-reactive protein,tumor necrosis factor-α and interleukin-6 (P ＜ 0.05),and decreased the area percentage of atherosclerotic lesions in aorta roots (15.6 ± 3.3 ％ vs.45.4 ± 9.8 ％,P ＜ 0.05) and increased the integrated optical density of CD31 in the arterial intima in high-fat diet mice(54.1±11.0％ vs.28.7±10.6％,P＜0.05)Conclusions AVE0991 can attenuate atherogenesis in ApoE-/-mice fed a high-fat diet,possibly via reducing inflammatory response,regulating the activity of nitric oxide synthases and improving endothelial functions.%目的 探讨AVE0991对载脂蛋白E基因敲除(ApoE-/-)小鼠血管内皮功能及动脉粥样硬化形成的影响. 方法 8周龄ApoE-/-雄性小鼠和C57BL/6J雄性小鼠数字抽签分为正常饮食组、高脂饮食组、高脂+AVE0991组各10只,分别给予普通饮食、高脂饮食、高脂饮食的基础上灌服AVE0991(0.58 μmol· kg-1·d-1).饲养12周后,检测各组小鼠血清中血脂水平、血管内皮功能指标,并采用油红O染色分析主动脉根部的动脉粥样硬化斑块大小,免疫组化分析血管内膜CD31的表达. 结果 AVE0991对高脂饮食组小鼠血脂无影响(P＞0.05).AVE0991降低高脂饮食组小鼠血清一氧化氮的生成,(76.8±34.4)μmol/L比(116.8±33.9)μmol/L(P＜0.05);对高脂饮食组小鼠血清中一氧化氮活性无影响(19.5±5.7) U/ml比(17.9±3.3)U/ml(P＞0.05);降低高脂饮食组小鼠血清中诱导型一氧化氮合酶的活性(9.0±2.3)U/ml比(12.7±3.2)U/ml(P＜0.05);增加高脂饮食组小鼠血管壁中磷酸化一氧化氮合成酶占诱生型一氧化氮合酶活性水平百分比(0.8±0.2)％比(0.6±0.2)％(P＜0.05);降低高脂饮食小鼠的血清C反应蛋白、白细胞介素6水平(均P＜0.05);降低高脂饮食小鼠主动脉动脉粥样硬化斑块占主动脉内膜面积百分比(15.6±3.3)％比(45.4±9.8)％(P＜0.05)、增加高脂饮食小鼠血管内膜CD31的相对光密度值(54.1±11.0)％比(28.7±10.6)％(P＜0.05). 结论 AVE0991可抑制ApoE-/-小鼠动脉粥样硬化的发展,其机制可能与抑制炎症反应,调节一氧化氮合酶活性,保护血管内皮功能相关.

摘要： 目的 观察糖尿病肾病(diabetic nephropathy,DN)肾活检组织中血管紧张素受体AT1、AT2和MAS受体表达情况,并探讨其与肾脏病理损伤的关系.方法 选取2004年1月至2017年7月在中日友好医院肾内科行肾穿刺活检病理诊断为DN的患者124例,其中病理分型为Ⅰ型+Ⅱa型15例,Ⅱb型26例,Ⅲ型76例,Ⅳ型7例.使用免疫组化染色评估肾活检组织中血管紧张素受体的表达情况.比较各型患者的临床资料和肾活检组织血管紧张素受体表达情况.结果 在不同病理分型的患者中,与Ⅰ+Ⅱa型、Ⅱb型及Ⅳ型相比,Ⅲ型肾小球、肾小管AT1受体表达显著增加.随着病理损伤的加重,肾脏血管AT1受体表达减少.肾小球AT2受体表达在Ⅱb型最高,随着病理损伤的加重,表达减少.与Ⅰ+Ⅱa型、Ⅲ型及Ⅳ型相比,Ⅱb型肾小管AT2受体表达显著增加.肾小球MAS受体表达在Ⅰ+Ⅱa型最高,Ⅲ型与Ⅱb型无明显差异,Ⅳ型与Ⅲ型相比,表达下降.肾小管和肾脏血管MAS受体表达与肾小球基本一致.结论 DN肾活检组织血管紧张素受体表达与肾脏病理改变存在一定的相关性,为深入认识肾素-血管紧张素系统(renin-angiotensin system,RAS)在DN中的作用提供了依据.%Objective To observe the expression of AT1,AT2 and MAS receptors in renal biopsy tissue from diabetic nephropathy (DN) patients,and to discuss its relationship with renal pathological injury.Methods A total of 124 patients diagnosed as DN by renal biopsy in our hospital from January 2004 to July 2017 were enrolled in our research (15 cases of class Ⅰ + Ⅱa,26 cases of class Ⅱb,76 cases of class Ⅲ and 7 cases of class Ⅳ).The expression of angiotensin receptors was evaluated by immunohistochemistry and analyzed by mean density.Clinical data,protein expression of AT1,AT2 and MAS receptors in renal biopsy tissue and its relationship with pathological injury were evaluated.Results Glomerular and tubular AT1 receptor expression in patients of class Ⅲ was significantly stronger than class Ⅰ + Ⅱa,Ⅱb and Ⅳ.Vascular AT1 receptor expression gradually weakened as the pathological injury was aggravating.Glomerular AT2 receptors expression in patients of class Ⅱb was strongest,glomerular AT2 receptors expression weakened as the pathological injury was aggravating.Tubular AT2 receptors expression in patients of class Ⅱb was significantly stronger than class Ⅰ + Ⅱa,Ⅲ and Ⅳ.Glomerular MAS receptor expression in patients of class Ⅰ + Ⅱ was strongest,it was no difference between class Ⅱb and Ⅲ,glomerular MAS receptor expression in patients of class Ⅳ was significantly weaker than class Ⅲ.Tubule and vascular MAS receptor expression were similar to glomeruli.Conclusions Expression of AT1,AT2 and MAS receptors in renal biopsy tissue is associated with pathologic injury in DN patients,which provides more evidence to elucidate the role of RAS in DN.

摘要： 目的 探讨血管紧张素Ⅱ(AngⅡ)、血管紧张素(1-7)[(Ang(1-7)]与急性冠状动脉综合征(ACS)的相关性.方法 采用前瞻性研究方法,收集ACS患者134例,同时选取健康人群30例作为对照组.检测所有患者血浆AngⅡ、Ang(1-7)水平及血清肌钙蛋白1(cTnⅠ)水平.比较ACS各分型组间上述指标差异,评价AngⅡ、Ang(1-7)对于ACS患者心肌梗死的诊断价值,并分析上述指标与ACS的相关性.结果 AngⅡ、Ang(1-7)与cTnⅠ在不稳定型心绞痛(UAP)、非ST段抬高型心肌梗死(NSTEMI)、ST段抬高心肌梗死(STEMI)及正常对照组之间差异存在统计学意义(P＜0.01);AngⅡ、Ang(1-7)与cTnⅠ呈正相关(P＜0.01),AngⅡ、Ang(1-7)及cTnⅠ对于ACS患者心肌梗死均具有诊断价值(P＜0.01),cTnⅠ尤为显著,进一步绘制ROC曲线提示AngⅡ、Ang(1-7)及cTnⅠ诊断界值分别为:51.23pg/ml、42pg/ml及0.3ng/ml(P＜0.01),AngⅡ、Ang(1-7)对于ACS患者心肌梗死的诊断效能优于cTnⅠ(P＜ 0.05),而AngⅡ与Ang(1-7)之间差异无统计学意义(P＞0.05).结论 不同分型ACS患者AngⅡ、Ang(1-7)及AngⅡ/Ang(1-7)比值有统计学意义,AngⅡ、Ang(Ⅰ-7)对于ACS患者病情评估具有指导意义.

摘要： 目的 探讨血管紧张素1-7[Ang-(1-7)]对高脂诱导的小鼠肝脏损伤的保护作用及潜在调节机制.方法将40只健康雄性C57BL/6小鼠随机分为正常组、高脂组、高脂+Ang-(1-7)组、Ang-(1-7)组,建模后分别检测每组小鼠血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)的水平,油红O染色检测小鼠肝脏脂质沉积,Western blotting检测肝脏中固醇调节元件结合蛋白(SREBP2)的表达水平.结果高脂组小鼠血清TC、TG、LDL水平均明显高于正常组和高脂+Ang-(1-7)组,差异均有统计学意义(P<0.05);高脂组小鼠肝脏脂质沉积明显,Western blotting提示SREBP2蛋白表达水平因高脂呈负反馈效应,Ang-(1-7)能够增强这一负反馈作用,使SREBP2蛋白表达水平进一步降低,有效阻断机体对脂质的吸收.结论Ang-(1-7)能够通过调节小鼠SREBP2的表达,从而减轻脂质沉积,发挥保护肝脏作用.

摘要： 目的 观察Toll样受体4(TLR4)在氧化低密度脂蛋白(ox-LDL)诱导人脐静脉内皮细胞发生氧化应激反应中的作用,并探讨血管紧张素(Ang)-(1-7)对上述反应的作用及其作用机制.方法 体外培养人脐静脉内皮细胞,并将细胞分为6组,分别为对照组(不干预)、ox-LDL组(以ox-LDL 75 mg/L干预)、ox-LDL+ Ang-(1-7)组[Ang-(1-7)1μmol/L预处理30 min后,以ox-LDL75 mg/L干预]、ox-LDL+ Ang-(1-7)+ A-779组[A-779(Mas受体阻断剂)1μmol/L预处理30 min,然后以Ang-(1-7)1 μmol/L预处理30 min,再以ox-LDL 75 mg/L干预]、ox-LDL+A-779组(A-779 1 μmol/L预处理30 min后,以ox-LDL 75 mg/L干预)、ox-LDL+ HTA125组[HTA125(TLR4特异性阻断抗体)10 μg/L预处理30 min后,以ox-LDL 75 mg/L干预].干预24 h后,分别以膜联蛋白V(Annexin V)-FITC/碘化丙啶(PI)双标记流式细胞术和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法(TUNEL)检测细胞凋亡,2',7'-二氯荧光黄双乙酸盐(DCFH-DA)标记法检测活性氧自由基(R OS)水平,实时荧光定量逆转录聚合酶链反应(RT-PCR)检测TLR4和NADPH氧化酶4 (NOX4)的mRNA表达水平,Western blot检测TLR4和NOX4的蛋白表达水平.结果 (1)AnnexinV-FITC/PI双标记流式细胞术显示,ox-LDL组的细胞凋亡比例高于对照组[(21.18±1.40)％比(1.59 ±0.26)％,P＜0.01],ox-LDL+ Ang-(1-7)组[(7.42±1.07)％]和ox-LDL+ HTA 125组[(9.19±1.01)％]的细胞凋亡比例均低于ox-LDL组(P均＜0.01),ox-LDL+ Ang-(1-7)+A-779组[(19.91±1.30)％]和ox-LDL+ A-779组[(20.47±0.95)％]的细胞凋亡比例均高于ox-LDL+ Ang-(1-7)组(P均＜0.01).(2)TUNEL法显示,ox-LDL组的细胞凋亡比例高于对照组[(10.83±0.77)％比(2.83±0.82)％,P＜0.01],ox-LDL+ Ang-(1-7)组[(3.66±0.54)％]和ox-LDL+ HTA125组[(4.97±0.60)％]的细胞凋亡比例均低于ox-LDL组(P均＜0.01),ox-LDL+ Ang-(1-7)+A-779组[(10.69±0.62)％]和ox-LDL+ A-779组[(11.43±0.42)％]的细胞凋亡比例均高于ox-LDL+ Ang-(1-7)组(P均＜0.01).(3)ox-LDL组的ROS水平高于对照组(0.093±0.014比0.053±0.011,P＜0.01),ox-LDL+ Ang-(1-7)组(0.063±0.011)和ox-LDL+ HTA125组(0.070±0.010)的ROS水平均低于ox-LDL组(P值分别＜0.01和0.05),ox-LDL+ Ang-(1-7)+A-779组(0.088±0.003)和ox-LDL+A-779组(0.095±0.005)的ROS水平均高于ox-LDL+ Ang-(1-7)组(P均＜0.01).(4)ox-LDL组NOX4的mRNA表达水平高于对照组(11.74±0.65比1.00±0.00,P＜0.01),ox-LDL+ Ang-(1-7)组(2.85±0.75)和ox-LDL+ HTA125组(5.57±0.52) NOX4的mRNA表达水平均低于ox-LDL组(P均＜0.01),ox-LDL+ Ang-(1-7)+A-779组(10.51 ±0.54)和ox-LDL+ A-779组(11.04±1.01) NOX4的mRNA表达水平均高于ox-LDL+ Ang-(1-7)组(P均＜0.01).ox-LDL组TLR4的mRNA表达水平高于对照组(27.60±1.86比1.00±0.00,P＜0.01),ox-LDL+ Ang-(1-7)组(8.00±1.03)和ox-LDL+HTA125组(14.83±0.97) TLR4的mRNA表达水平均低于ox-LDL组(P均＜0.01),ox-LDL+Ang-(1-7)+ A-779组(24.81 ±2.19)和ox-LDL+ A-779组(26.64±0.65) TLR4的mRNA表达水平均高于ox-LDL+Ang-(1-7)组(P均＜0.01).(5)ox-LDL组NOX4的蛋白表达水平高于对照组(0.61±0.09比0.23±0.02,P＜0.01),ox-LDL+ Ang-(1-7)组(0.27±0.03)和ox-LDL+ HTA125组(0.22±0.02) NOX4的蛋白表达水平均低于ox-LDL组(P均＜0.01),ox-LDL+ Ang-(1-7)+A-779组(0.58±0.06)和ox-LDL+ A-779组(0.61±0.03) NOX4的蛋白表达水平均高于ox-LDL+Ang-(1-7)组(P均＜0.01).ox-LDL组TLR4的蛋白表达水平高于对照组(0.18 ±0.02比0.08±0.01,P＜0.01),ox-LDL+ Ang-(1-7)组(0.07±0.01)和ox-LDL+ HTA125组(0.09±0.01)TLR4的蛋白表达水平均低于ox-LDL组(P均＜0.01),ox-LDL+Ang-(1-7)+A-779组(0.18±0.02)和ox-LDL+A-779组(0.20±0.02) TLR4的蛋白表达水平均高于ox-LDL+ Ang-(1-7)组(P均＜0.01).结论 TLR4在ox-LDL诱导人脐静脉内皮细胞损伤中起介导作用,Ang-(1-7)通过特异性Mas受体发挥对细胞的保护作用.%Objective To explore the role and related mechanisms of angiotensin-(1-7) (Ang(1-7)) on Toll-like receptor 4 (TLR4) mediated oxidized low-density lipoprotein (ox-LDL)-induced oxidative stress in human umbilical vein endothelial cells (HUVECs).Methods HUVECs were cultured in vitro and divided into six groups:the control group (normal medium),the ox-LDL group (treated with 75 mg/L ox-LDL),the ox-LDL +Ang-(1-7) group (1 μ mol/L Ang-(1-7) pretreated for 30 minutes,then intervened with 75 mg/L ox-LDL),the ox-LDL +Ang-(1-7) + A-779 group (1 μmol/L A-779 (Mas receptor) pretreated for 30 minutes,1 μmol/L Ang-(1-7) pretreated for 30 minutes,then intervened with 75 mg/L ox-LDL),the ox-LDL + A-779 group (1 μmol/L A-779 pretreated for 30 minutes,then intervened with 75 mg/L ox-LDL),the ox-LDL + HTA125 group (10 μg/L HTA125 (TLR4-blocking antibody) pretreated for 30 minutes,then intervened with 75 mg/L ox-LDL).The corresponding index was detected after 24 hours after intervention.Apoptosis of cells were detected by Annexin V-FITC/PI double staining flow cytometry and transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL).The generation of reactive oxygen species (ROS),products in oxidative stress,were detected by DCFH-DA staining.The mRNA and protein expression levels of NADPH oxidase 4 (NOX4) and TLR4 were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analysis respectively.Results (1) The results of Annexin V-FITC/PI double staining flow cytometry showed that the proportion of apoptotic cells was higher in ox-LDL group than in control group ((21.18-± 1.40)％ vs.(1.59 ± 0.26) ％,P ＜ 0.01),lower in ox-LDL +Ang-(1-7) group ((7.42 ± 1.07) ％) and ox-LDL + HTA125 group((9.19 ± 1.01)％) than in ox-LDL group (both P ＜ 0.01),higher in ox-LDL + Ang-(1-7) + A-779 group ((19.91 ± 1.30) ％) and ox-LDL + A-779 group ((20.47 ± 0.95) ％) than in ox-LDL + Ang-(1-7) group (both P ＜ 0.01).(2) The TUNEL results showed that the proportion of apoptotic cells was higher in ox-LDL group than in control group ((10.83 ± 0.77) ％ vs.(2.83 ± 0.82) ％,P ＜ 0.01),lower in ox-LDL + Ang-(1-7) group ((3.66 ± 0.54) ％) and ox-LDL + HTA125 group((4.97 ± 0.60) ％) than in ox-LDL group(both P ＜ 0.01),higher in ox-LDL + Ang-(1-7) + A-779 group ((10.69 ± 0.62) ％) and ox-LDL + A-779 group ((1 1.43 ± 0.42) ％) than in ox-LDL +Ang-(1-7) group (both P ＜ 0.01).(3) ROS level was higher in ox-LDL group than in control group(0.093 ±0.014 vs.0.053 ±0.011,P ＜0.01),lower in ox-LDL +Ang-(1-7) group (0.063 ± 0.011,P ＜ 0.01) and ox-LDL + HTA125 group (0.070 ± 0.010,P ＜0.05) than in ox-LDL group,higher in ox-LDL +Ang-(1-7) + A-779 group(0.088 ±0.003) and ox-LDL + A-779 group (0.095 ± 0.005) than in ox LDL + Ang-(1-7) group (both P ＜ 0.01).(4) The mRNA expression level of NOX4 was higher in ox-LDL group than in control group(11.74 ±0.65 vs.1.00 ± 0.00,P ＜0.01),lower in ox-LDL +Ang-(1-7) group (2.85 ±0.75)and ox-LDL + HTA125 group(5.57 ± 0.52) than in ox-LDL group(both P ＜0.01),higher in ox-LDL +Ang-(1-7) + A-779 group(10.51 ± 0.54) and ox-LDL + A-779 group (11.04 ± 1.01) than in ox-LDL +Ang-(1-7) group (both P ＜ 0.01),higher in ox-LDL group than in control group(27.60 ± 1.86 vs.1.00 ±0.00,P ＜0.01),lower in ox-LDL + Ang-(1-7) group (8.00 ± 1.03)and ox-LDL + HTA125 group (14.83 ± 0.97) than in ox-LDL group (both P ＜ 0.01),higher in ox-LDL +Ang-(1-7) + A-779 group (24.81 ± 2.19) and ox-LDL + A-779 group (26.64 ± 0.65) than in ox-LDL +Ang-(1-7) group (both P ＜ 0.01).(5) The protein expression level of NOX4 was higher in ox-LDL group than in control group (0.61 ±0.09 vs.0.23 ±0.02,P ＜0.01),lower in ox-LDL + Ang-(1-7) group (0.27 ± 0.03) and ox-LDL + HTA125 group (0.22 ± 0.02) than in ox-LDL group(both P ＜ 0.01),higher in ox-LDL + Ang-(1-7) + A-779 group (0.58 ± 0.06) and ox-LDL + A-779 group(0.61 ± 0.03) than in ox-LDL +Ang-(1-7) group (both P ＜ 0.01).The protein expression level of TLR4 was higher in ox-LDL group than in control group(0.18 ±0.02 vs.0.08 ±0.01,P ＜0.01),lower in ox-LDL + Ang-(1-7) group (0.07 ± 0.01) and ox-LDL + HTA125 group (0.09 ± 0.01) than in ox-LDL group(both P ＜ 0.01),higher in ox-LDL + Ang (1 7) + A-779 group (0.18 ± 0.02) and ox-LDL + A-779 group(0.20 ± 0.02) than in ox-LDL + Ang-(1-7) group (both P ＜ 0.01).Conclusion TLR4 mediated the ox-LDL induced injury in HUVECs,and Ang-(1-7) could attenuate ox-LDL induced injury in HUVECs by modulating the specific Mas receptors.

摘要： 目的 观察血管紧张素1-7[Ang-(1-7)]对血管紧张素Ⅱ(AngⅡ)诱导的人脐静脉内皮细胞中细胞间黏附分子1(ICAM-1)和血管细胞黏附分子1(VCAM 1)表达的影响及作用机制是否与CD40及CD40配体(CD40L)通路有关.方法 人脐静脉内皮细胞培养后,分6组:对照组;AngⅡ组;低、中和高剂量组[Ang(1-7)10、100和1000nmol/L预处理];阻断剂组(A-779预处理).用RT-PCR法检测ICAM-1、VCAM-1和CD40、CD40L mRNA表达.结果 与对照组比较,AngⅡ组ICAM-1、VCAM-1和CD40、CD40L mRNA表达显著升高(P＜0.05);与AngⅡ组比较,低、中和高剂量组ICAM-1、VCAM-1和CD40、CD40LmRNA的表达逐渐下降(P＜0.05),其中ICAM-1、VCAM-1 mRNA表达分别下降25％、58％、69％和30％、53％、62％;CD40、CD40L mRNA表达分别下降35％、48％、61％和26％、54％、68％;阻断剂组与AngⅡ组上述指标比较无显著差异(P＞0.05).结论 Ang-(1-7)可以抑制炎症通路CD40/CD40L活化,进而下调黏附分子ICAM-1、VCAM-1的表达;Ang-(1-7)的抗炎机制是首先与Mas受体结合,进而发挥抑制CD40/CD40L通路的作用.%Objective To study the inhibitory effect of Ang 1-7 on expression of Ang Ⅱ-induced intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in cultured human umbilical vein endothelial cells (HUVEC) and whether its mechanism is related with the CD40/CD40L pathway.Methods Cultured HUVEC were divided into control group,Ang Ⅱ group,low AngⅡ dose (10 nmol/L) group,medium AngⅡ dose (100 nmol/L) group,high AngⅡ dose (1000 nmol/L) group and blocker (A-779) group.Expressions of ICAM-1,VCAM-1,CD40/CD40L mRNA were detected by RT-PCR.Results The expression levels of ICAM-1,VCAM-1,CD40/CD40L mRNA were significantly higher in Ang Ⅱ group than in control group (P＜0.05)and were significantly lower in low AngⅡ dose group,medium Ang Ⅱ dose group and high Ang Ⅱ dose group than in Ang Ⅱ group (P＜0.05).The expression of ICAM-1 and VCAM-1 decreased by 25％,58％,69％ and 30％,53％,62％,and that of CD40/CD40L mRNA decreased by 35％,48％,61％ and 26 ％,54％,68％.No significant difference was found in the expressions of ICAM-1,VCAM 1,CD40/CD40L mRNA between Ang Ⅱ group and blocker group (P＞0.05).Conclusion Ang 1-7 can inhibit the activation of CD40/CD40L pathway and downregulate the expression of ICAM-1 and VCAM-1 in HUVEC by binding to their specific receptor Mas.

摘要： 目的：研究慢性乙型肝炎和肝硬化患者肾素-血管紧张素系统（RAS）中血管紧张素Ⅱ（AngⅡ）、血管紧张素（1-7）[Ang（1-7）]及AngⅡ/Ang（1-7）比值的变化，探讨其在肝纤维化发病过程中的意义。方法收集20例慢性乙型肝炎患者、60例乙型肝炎肝硬化患者和20例健康对照者的一般临床资料及血浆标本，采用酶联免疫吸附法测定血浆中 AngⅡ、Ang（1-7）的水平，分析AngⅡ、Ang（1-7）及AngⅡ/Ang（1-7）在各组之间的表达差异。结果肝硬化患者血浆AngⅡ、Ang（1-7）水平及AngⅡ/Ang（1-7）比值分别为（105.88±53.56）pg/ml，（77.95±27.43）pg/ml，1.34±0.48，均显著高于乙型肝炎组和对照组[（59.98±12.97）pg/ml、（21.53±18.27）pg/ml，（62.45±11.24）pg/ml、（27.06±12.76）pg/ml，0.97±0.16、0.72±0.39；均P＜0.01]；肝硬化患者Child-Pugh A级至C级AngⅡ、Ang（1-7）水平及AngⅡ/Ang（1-7）的比值逐渐升高，各组之间差异有统计学意义（P＜0.05）；AngⅡ/Ang（1-7）比值与Child-Pugh评分呈正相关（r=0.499，P＜0.01）。结论随着肝纤维化或肝硬化患者的病情进展，AngⅡ/Ang（1-7）的比值逐渐增加，其水平对慢性肝病患者的病情评估具有指导意义。%ObjectiveTo study the significance in the progress of liver fibrosis, through exploring the change of plasma angiotensinⅡ (AngⅡ), angiotensin (1-7)[Ang (1-7)] and ratio of AngⅡ/Ang (1-7) in patients with chronic hepatitis B (CHB) and HBV-related cirrhosis.Methods The plasma samples and general clinical data of 20 CHB patients, 60 HBV associated cirrhosis patients and 20 healthy controls were collected in this study. The levels of the AngⅡ and Ang (1-7) were detected by enzyme linked immunosorbent assay (ELISA), statistical method was used to analyze the different expressions of AngⅡ, Ang (1-7) and AngⅡ/Ang (1-7) ratio in different groups.Results The levels of AngⅡ, Ang (1-7) and AngⅡ/Ang (1-7) ratio in cirrhosis groups were (105.88±53.56)pg/ml, (77.95±27.43)pg/ml, 1.34±0.48, respectively, which were significantly higher than those in hepatitis B and normal controls, (59.98±12.97)pg/ml and (21.53±18.27)pg/ml, (62.45±11.24)pg/ml and (27.06±12.76)pg/ml, 0.97±0.16 and 0.72±0.39, respectively,P<0.01; The levels of AngⅡ, Ang (1-7) and AngⅡ/Ang (1-7) ratio in cirrhosis gradually elevated from Child-Pugh A group to C group and their had significant difference, P<0.05. There was a positive correlation between the level of AngⅡ/Ang (1-7) ratio and Child-Pugh score (r=0.499,P<0.01).ConclusionThe levels of AngⅡ/Ang (1-7) ratio increase significantly with the progress of liver fibrosis and cirrhosis, the level has the guiding significance in evaluation of severity of cirrhosis.

摘要： 本发明公开了血管紧张素、血管紧张素醋酸盐的制备方法。该血管紧张素的制备方法包括下述步骤：采用高效液相反相色谱法将血管紧张素粗品溶液依次进行反相纯化、反相脱盐，即可；高效液相反相色谱法的填料为苯乙烯‑二乙烯基苯(PS‑DVB)共聚物。本发明将反相纯化和反相脱盐联用，设计出聚合物填料苯乙烯‑二乙烯基苯的最新应用，可以大批量制备血管紧张素和血管紧张素醋酸盐。

摘要： 本发明公开一种短肽及其衍生物作为模板分子的应用及基于印迹技术制备血管紧张素合成受体的方法。所述模板分子包括血管紧张素Ⅱ的氮端或碳端的任何一段肽键及其衍生物、或血管紧张素Ⅰ的氮端或碳端的任何一段肽键及其衍生物中的一种。所述应用是以上述模板分子印迹用于制备血管紧张素合成受体。血管紧张素受体由模板分子、功能单体、交联剂和表面活性剂等按一定比例混合，加入引发剂后聚合制备。该受体生物相容性好，可高选择性地捕获中和血管紧张素Ⅱ和血管紧张素Ⅰ，阻断血管紧张素Ⅱ与血管紧张素受体（AT1）以及血管紧张素Ⅰ与血管紧张素转换酶（ACE）作用，从而达到控制血压的目的。该受体也可用于血管紧张素Ⅰ或Ⅱ的分离富集及测定。

摘要： 本发明所提供的组合物可用于治疗一种肾素—血管紧张素醛固酮系统相关疾病。组合物包括肾素—血管紧张素醛固酮系统抑制剂和硫辛酸化合物，以及其他可用治疗患者高血压，中风，代谢综合征，或其他肾素—血管紧张素醛固酮系统相关的疾病的治疗药剂。该组合物也有助于改善患者的血管舒张，降低蛋白尿，降低胰岛素抵抗。本发明还提供了利用本发明的组合物进行治疗的药物组合物和方法。

摘要： 本发明涉及免疫学检测技术领域，尤其涉及人工修饰的血管紧张素II及血管紧张素II酶标记物。本发明提供了人工修饰血管紧张素II，其在血管紧张素II的N端或C端修饰有X(G

摘要： 本发明涉及一种液相色谱串联质谱法同时测定干血滤纸片中血管紧张素Ⅰ、血管紧张素Ⅱ、醛固酮含量，属于医学检测领域，本发明采用液相色谱质谱联用仪进行检测，以以AngⅠ、AngⅡ、ALD的标准工作液与内标工作液浓度的比值为横坐标，各自标准工作液与内标工作液的色谱图峰面积比值为纵坐标绘制标准曲线。需要检测待测样品时使用液相色谱质谱联用仪测出待测样品峰面积，然后通过S1步骤的标准曲线进行定量，计算出待测样品中AngⅠ、AngⅡ、ALD的含量。本发明方法所采用的前处理方法简单、便捷、耗时短、所需采血量较少，且可以同时检测三种物质。

摘要： 本发明涉及一种血管紧张素I氨基酸片段的衍生物，选自本发明提供的14种序列中的任一种；本发明还涉及一种血管紧张素I抗原，该抗原由上述血管紧张素I氨基酸片段的衍生物与活化载体反应制得；以该抗原接种健康动物可以获得血管紧张素I抗体，利用该血管紧张素I抗体可以实现血管紧张素I的高效检测。

摘要： 本发明涉及一种血管紧张素II氨基酸片段的衍生物，其序列选自：a)Cys-R-Val-Tyr-Ile-His-Pro-Phe；b)Cys-R-Tyr-Ile-His-Pro-Phe；c)Cys-R-Ile-His-Pro-Phe；d)Cys-Val-Tyr-Ile-His-Pro-Phe；e)Cys-Tyr-Ile-His-Pro-Phe；以及f)Cys-Ile-His-Pro-Phe；本发明还涉及一种血管紧张素II抗原，该抗原由上述血管紧张素II氨基酸片段的衍生物与活化载体反应制得；以该抗原接种健康动物可以获得血管紧张素II抗体，利用该血管紧张素II抗体可以实现血管紧张素II的高效检测。

摘要： 本发明公开了血管紧张素、血管紧张素醋酸盐的制备方法。该血管紧张素的制备方法包括下述步骤：采用高效液相反相色谱法将血管紧张素粗品溶液依次进行反相纯化、反相脱盐，即可；高效液相反相色谱法的填料为苯乙烯-二乙烯基苯(PS-DVB)共聚物。本发明将反相纯化和反相脱盐联用，设计出聚合物填料苯乙烯-二乙烯基苯的最新应用，可以大批量制备血管紧张素和血管紧张素醋酸盐。

摘要： 本发明是关于治疗征候的方法，所述征候确定受到AT1调节效果的抑制作用影响，但仍维持血管紧张素II的AT2受体的调节效果，以及受到ACE抑制作用影响，因此亦受到增加舒缓激肽调节效果影响，例如降低中风、急性心肌梗塞或心血管死亡的发生率，以及所述征候与在上皮下区域增加AT1受体，或在上皮中增加AT2受体有关，包括共同－给药有效数量的血管紧张素II拮抗剂和ACE抑制剂；含有血管紧张素II拮抗剂和ACE抑制剂的药物组合物；以及血管紧张素II拮抗剂和ACE抑制剂在制造一致的药物组合物上的用途。

摘要： 本发明涉及血管紧张素转换酶活性的测定方法及其诊断试剂盒。发明应用人工合成底物FAPGG直接与血管紧张素转换酶作用，生成在340nm没有吸收峰的呋喃基－丙烯酰－苯丙氨酸，通过检测340nm吸光度的下降速度定量反映出样品中血管紧张素转换酶的活性大小。该方法特异性高，不受内、外源物质的污染，测试结果精确、准确性好，制成的试剂稳定性好，便于长期储存。该方法在普通紫外/可见光分析仪或者半自动/全自动生化分析仪上便可快速检测，不需要特殊或额外仪器，测试成本低廉，便于推广应用。