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氯沙坦及A779对糖尿病心肌病大鼠心肌间质纤维化的影响 被引量:4
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作者 胡圣 张绪洪 +3 位作者 董波 朱梅 张月辉 于庆涛 《山东大学学报(医学版)》 CAS 北大核心 2008年第4期362-365,共4页
目的观察氯沙坦对糖尿病心肌病大鼠心肌间质纤维化的影响并探讨其机制。方法将39只雄性Wistar大鼠给予链脲佐菌素(STZ)55 mg/kg一次性腹腔注射12周后,将血糖>16.7 mol/L且具有多饮、多食、多尿现象的36只大鼠纳入实验。实验大鼠随机... 目的观察氯沙坦对糖尿病心肌病大鼠心肌间质纤维化的影响并探讨其机制。方法将39只雄性Wistar大鼠给予链脲佐菌素(STZ)55 mg/kg一次性腹腔注射12周后,将血糖>16.7 mol/L且具有多饮、多食、多尿现象的36只大鼠纳入实验。实验大鼠随机分为糖尿病心肌病(DCM)组、氯沙坦组和A779+氯沙坦组,每组12只。给予氯沙坦组大鼠氯沙坦10 mg/(kg.d)灌胃,给予A779+氯沙坦组大鼠氯沙坦10 mg/(kg.d)灌胃和血管紧张素-(1-7)受体拮抗剂A779 100 ng/(kg.d)尾静脉注射,给予DCM组大鼠等量生理盐水灌胃,治疗持续4周。第16周末采用心脏超声、Masson染色及RT-PCR的方法测定大鼠的左室舒张末期内径(LVIDd)、左室收缩末期内径(LVIDs)、短轴缩短率(FS)、左室射血分数(LVEF)、E/A(E峰/A峰)、左室心肌胶原含量、ACE2 mRNA的表达。结果与DCM组比较,氯沙坦组和A779+氯沙坦组大鼠的LVIDs、LVIDd降低(P<0.01),E/A、FS、LVEF升高(P<0.01),左室胶原含量减轻(P<0.01),ACE2 mRNA表达增高(P<0.01);与氯沙坦组比较,A779+氯沙坦组大鼠LVIDs、LVIDd升高(P<0.05),E/A、FS、LVEF降低(P<0.05),左室胶原含量升高(P<0.05),ACE2 mRNA表达无明显差异。结论氯沙坦通过Ang-(1-7)途径减少纤维化及改善心功能。 展开更多
关键词 氯沙坦 血管紧张素-(1-7) 血管紧张素转换酶-2 a779 糖尿病 心肌病 大鼠 WISTAR
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血管紧张素1-7降低脂肪细胞氧化应激增加脂联素表达 被引量:7
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作者 刘畅 曹曦 +3 位作者 杨芳远 张雪莲 袁明霞 杨金奎 《首都医科大学学报》 CAS 2014年第1期45-50,共6页
目的研究血管紧张素(1-7)[Ang-(1-7)]/Mas轴对于高糖培养脂肪细胞氧化应激及脂联素表达的作用。方法用前脂肪细胞株3T3L1诱导分化成成熟细胞,分别在培养基中加入外源性的Ang-(1-7)10-9mol/L,Mas受体抑制剂A779 10-6mol/L,同时加入Ang-(1... 目的研究血管紧张素(1-7)[Ang-(1-7)]/Mas轴对于高糖培养脂肪细胞氧化应激及脂联素表达的作用。方法用前脂肪细胞株3T3L1诱导分化成成熟细胞,分别在培养基中加入外源性的Ang-(1-7)10-9mol/L,Mas受体抑制剂A779 10-6mol/L,同时加入Ang-(1-7)及A779。分别用DHE荧光探针通过流式细胞术及用NBT染色法检测脂肪细胞内活性氧(ROS)含量。实时定量PCR方法检测脂联素及炎性反应因子的表达。无血清培养基培养脂肪细胞2 h后分别加入葡萄糖氧化酶(GO)50mU/mL、100 mU/mL作用12 h建立氧化应激模型,研究Ang-(1-7)对于脂肪细胞氧化应激的作用及对脂联素表达的影响。结果①Ang-(1-7)通过Mas受体降低脂肪细胞活性氧的产生。Mas受体抑制剂A779可逆转此作用。②构建氧化应激模型,脂肪细胞中的脂联素表达水平随着葡萄糖氧化酶浓度的增高而减少。③加入Ang-(1-7)可以逆转氧化应激导致的脂联素表达降低,抑制剂A779可以对抗Ang-(1-7)的这一作用。④Ang-(1-7)对于白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的mRNA表达水平没有影响。结论 Ang-(1-7)/Mas轴可以减少氧化应激产生的活性氧水平。Ang-(1-7)/Mas轴对氧化应激的保护作用可以增加抗胰岛素抵抗因子脂联素的表达。 展开更多
关键词 血管紧张素(1-7) a779 氧化应激 脂联素
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血管紧张素1-7抑制剂对糖代谢的影响 被引量:1
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作者 史婷婷 马亚红 杨金奎 《首都医科大学学报》 CAS 北大核心 2009年第4期455-458,共4页
目的研究血管紧张素1-7Ang(1-7)的抑制剂A779对胰岛功能及其他代谢指标的影响从而为研究Ang(1-7)在糖尿病及其合并症中的作用提供新的思路。方法对c57bl/6小鼠置入皮下泵持续给予A779干预,干预结束后行腹腔糖耐量试验、胰岛素耐量试验... 目的研究血管紧张素1-7Ang(1-7)的抑制剂A779对胰岛功能及其他代谢指标的影响从而为研究Ang(1-7)在糖尿病及其合并症中的作用提供新的思路。方法对c57bl/6小鼠置入皮下泵持续给予A779干预,干预结束后行腹腔糖耐量试验、胰岛素耐量试验及胰岛素水平测定评价干预对糖代谢的影响,并测定血压、血脂及血管紧张素Ⅱ的水平,评价干预对其他代谢指标的影响。结果A779干预组的空腹胰岛素水平明显高于对照组,差异有统计学意义;胰岛素抵抗指数和胰岛素分泌指数明显高于对照组,差异有统计学意义。结论A779对糖耐量及胰岛素基础分泌产生负面影响,提示Ang(1-7)可能对胰岛功能具有保护作用。 展开更多
关键词 血管紧张素转化酶2 血管紧张素1-7 a779 胰岛功能
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AngⅡ/Ang-(1-7)/Mas系统通路与脑心综合征关系的实验研究 被引量:2
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作者 王娜 夏青 +1 位作者 赵剑 王玲 《哈尔滨医科大学学报》 CAS 北大核心 2012年第3期207-211,共5页
目的研究AngⅡ/Ang-(1-7)/Mas系统通路在脑心综合征发生及发展中的作用,探讨脑心综合征的发病机制。方法健康成年雄性Wistar大鼠64只,随机分为空白对照组、模型对照组、氯沙坦组、氯沙坦+A779组,每组内再分别分为4 h组、24 h组(n=8)。... 目的研究AngⅡ/Ang-(1-7)/Mas系统通路在脑心综合征发生及发展中的作用,探讨脑心综合征的发病机制。方法健康成年雄性Wistar大鼠64只,随机分为空白对照组、模型对照组、氯沙坦组、氯沙坦+A779组,每组内再分别分为4 h组、24 h组(n=8)。用线栓法栓塞大脑中动脉制作脑梗死模型,监测各组大鼠心电图。脑氯化三苯基四氮(TTC)染色确定模型是否成功。化学发光法检测组织和血浆中血管紧张素Ⅱ(AngⅡ)的含量,用酶联免疫吸附法(ELISA)法检测组织和血浆中血管紧张素1-7(Ang-(1-7))的含量。用苏木素伊红染色(HE)观察各组大鼠心肌损伤程度。结果模型对照组心肌损伤严重,氯沙坦组心肌损伤有所减轻。氯沙坦+A779组心肌损伤较氯沙坦组较重。心肌损伤程度随着时间的延长相应加重。模型对照组血浆中AngⅡ的含量相比空白对照组增加(P<0.01),氯沙坦组AngⅡ的含量相比模型对照组显著增加(P<0.01),氯沙坦+A779组AngⅡ的含量与氯沙坦组相比显著降低(P<0.01)。模型对照组血浆中Ang-(1-7)的含量相比空白对照组显著降低(P<0.01),氯沙坦组Ang-(1-7)的含量相比模型对照组升高(P<0.01),氯沙坦+A779组Ang-(1-7)的含量相比氯沙坦组降低(P<0.01)。血浆AngⅡ、Ang-(1-7)的含量分别随着时间的延长相应增加(P<0.01)。心肌局部AngⅡ、Ang-(1-7)的含量变化趋势分别与血浆中AngⅡ、Ang-(1-7)含量的变化趋势一致。结论 Ang-(1-7)通过Ang-(1-7)特异性受体(D-Ala-7-Ang-(1-7),Mas)参与脑心综合征的发生及发展,并对脑梗所致的心肌损伤起到保护作用。 展开更多
关键词 AngⅡ/Ang-(1-7)/Mas系统通路 脑心综合征 AngⅡ Ang-(1-7) a779
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Protective Effect of Angiotensin(1-7) on Silicotic Fibrosis in Rats 被引量:5
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作者 ZHANG Bo Nan XU Hong +3 位作者 GAO Xue Min ZHANG Gui Zhen ZHANG Xin YANG Fang 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2019年第6期419-426,共8页
Objective Silicosis, caused by inhalation of silica dust, is the most serious occupational disease in China and the aim of present study was to explore the protective effect of Ang(1-7) on silicotic fibrosis and myofi... Objective Silicosis, caused by inhalation of silica dust, is the most serious occupational disease in China and the aim of present study was to explore the protective effect of Ang(1-7) on silicotic fibrosis and myofibroblast differentiation induced by Ang II. Methods HOPE-MED 8050 exposure control apparatus was used to establish the rat silicosis model. Pathological changes and collagen deposition of the lung tissue were examined by H.E. and VG staining, respectively. The localizations of ACE2 and α-smooth muscle actin(α-SMA) in the lung were detected by immunohistochemistry. Expression levels of collagen type I, α-SMA, ACE2, and Mas in the lung tissue and fibroblasts were examined by western blot. Levels of ACE2, Ang(1-7), and Ang II in serum were determined by ELISA. Co-localization of ACE2 and α-SMA in fibroblasts was detected by immunofluorescence. Results Ang(1-7) induced pathological changes and enhanced collagen deposition in vivo. Ang(1-7) decreased the expressions of collagen type I and α-SMA and increased the expressions of ACE2 and Mas in the silicotic rat lung tissue and fibroblasts stimulated by Ang II. Ang(1-7) increased the levels of ACE2 and Ang(1-7) and decreased the level of Ang II in silicotic rat serum. A779 enhanced the protective effect of Ang(1-7) in fibroblasts stimulated by Ang II. Conclusion Ang(1-7) exerted protective effect on silicotic fibrosis and myofibroblast differentiation induced by Ang II by regulating ACE2-Ang(1-7)-Mas axis. 展开更多
关键词 SILICOSIS Ang II MYOFIBROBLASTS Ang(1-7) a779
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Neuroprotective Effects of Mas-receptor Ligands in an Experimental Rat Glaucoma
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作者 Anu Vaajanen Jooseppi Puranen +2 位作者 Giedrius Kalesnykas Heikki Vapaatalo Hannu Uusitalol 《Journal of Pharmacy and Pharmacology》 2014年第2期114-122,共9页
Objectives: Ocular effects of Mas-receptor ligands were studied in an experimental rat glaucoma. Elevated IOP (intraocular pressure) was induced unilaterally by laser photocoagulation of the episcleral and limbal v... Objectives: Ocular effects of Mas-receptor ligands were studied in an experimental rat glaucoma. Elevated IOP (intraocular pressure) was induced unilaterally by laser photocoagulation of the episcleral and limbal veins in anesthetized rats. A Mas-receptor agonist (Ang (1-7)) and an antagonist (A779) were administered intravitreally in the glaucomatous eye. lOP was measured by a rebound tonometer. Effects of the treatment on RGCL (retinal ganglion cell layer) were determined stereologically and on the axons of optic nerve by a modified Gallyas silver-staining method. Key findings: Mean IOP during the 14 days follow-up in the solvent treated glaucoma eyes (n = 18) was 28.7 -4- 1.9 mmHg vs. the fellow eyes 11.0 4- 0.3 mmHg. A significant axon damage was detected in the glaucomatous eyes vs. the fellow normotensive eye. The Mas-receptor ligands did not influence high IOP resulted by laser treatment, Despite of the ineffectiveness on lOP, Ang (1-7) protected RGCL cells as determined by stereology (P = 0.016). No significant effects in Gallyas silver-staining were found. Summary: Intravitreally administered Ang (1-7) showed a significant protective effect against neuronal damage. The present and our previous studies suggest that stimulation of Mas-receptor may have therapeutic potential to treat glaucoma. 展开更多
关键词 Mas-receptor Ang (1-7) a779 experimental glaucoma RAT intraocular pressure neuroprotection.
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