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替米沙坦对高血压大鼠血管前纤维蛋白1及ERK磷酸化水平的影响
  • 期刊名称:心血管康复医学杂志
  • 时间:0
  • 页码:166-169
  • 分类:R544.6[医药卫生—心血管疾病;医药卫生—临床医学;医药卫生—内科学]
  • 作者机构:[1]上海交通大学医学院附属瑞金医院医学基因组学国家重点实验室,上海200025, [2]上海市高血压研究所,上海市高血压重点实验室, [3]上海交通大学医学院附属瑞金医院临床心理科
  • 相关基金:国家自然科学基金(81170246&30973522); 上海市浦江人才计划项目(11PJ1408300); 上海交通大学SMC“晨星青年学者奖励计划”(A类); 上海交通大学医学院“新百人计划”项目
  • 相关项目:Profilin-1介导高血压血管平滑肌细胞增殖及ACE2调控作用研究
中文摘要:

目的:探讨高血压状态下血管组织前纤维蛋白-1(Profilin-1)-信号转导和转录激活因子-3(STAT3)信号改变以及厄贝沙坦干预对该信号通路与氧化应激水平的影响。方法:采用10周龄C57/B6小鼠,经血管紧张素II(Ang II)诱导为高血压,分为高血压组(8只,安慰剂治疗)和厄贝沙坦组(8只,每天厄贝沙坦50mg/kg治疗),另选正常血压小鼠(8只)为正常对照组。测量两周后血压水平,以Western印迹检测小鼠主动脉组织中Profilin-1表达及STAT3磷酸化水平,硫代巴比妥酸比色法测定丙二醛(MDA)含量。结果:与正常对照组相比,高血压组小鼠血压水平明显升高[收缩压:(104±4.4)mmHg比(159±6.2)mmHg],主动脉组织中Profi-lin-1蛋白表达[(1.00±0.08)比(2.91±0.12)]、STAT3磷酸化[(1.00±0.09)比(1.95±0.11)]以及MDA[(72.8±8.5)nmol/g protein比(165.2±13.6)nmol/g protein]水平明显增加(P均〈0.01),而厄贝沙坦组血压明显下降[收缩压:(130±4.8)mmHg,P〈0.01],主动脉组织Profilin-1表达(1.53±0.07)和STAT3磷酸化(1.27±0.08)水平显著降低,伴有MDA含量显著下降[(103.7±10.1)nmol/g protein],P均〈0.05。结论:高血压状态下存在血管Profilin-1-STAT3信号上调,伴有氧化应激增强,而厄贝沙坦干预降低高血压小鼠血管Profilin-1表达及STAT3磷酸化水平,促使血管氧化应激水平改善,可降低血压。

英文摘要:

Objective:To investigate changes of vascular tissue Profilin-1-signal transducer and activator of transcription 3(STAT3)signaling and influence of irbesartan on it and oxidative stress level in hypertension.Methods: The 10-week C57/B6mice were infused with angiotensin II to establish hypertensive animal model.They were divided into hypertension group(n=8,received placebo treatment)and irbesartan group(n=8,received irbesartan 50mg/kg everyday).Another eight mice with normal hypertension were regard as normal control group.Blood pressure was measured after two weeks;Western blotting method was used to measure levels of Profilin-1expression and STAT3phosphorylation in mice aortic tissue;thiobarbituric acid colorimetry was used to measure concentration of malonyl diadehyde(MDA).Results:Compared with normal control group,there were significant increase in blood pressure[systolic blood pressure(SBP):(104±4.4)mmHg vs.(159±6.2)mmHg],Profilin-1 protein expression in aortic tissue [(1.00±0.08) vs.(2.91±0.12)],STAT3phosphorylation [(1.00±0.09) vs.(1.95±0.11)] and MDA [(72.8±8.5) nmol/g pr otein vs.(165.2±13.6) nmol/g p rotein ] in hypertension group,P0.01all.After irbesartan treatment,there were significant decrease in blood pressure [ SBP :(130±4.8) mmHg,P0.01 ],Profilin-1expression in aortic tissue(1.53±0.07),STAT3phosphorylation(1.27±0.08) and MDA concentration [(103.7±10.1) nmol/g p rotein ] in irbesartan group,P0.05all.Conclusion:There is upregulated vascular Profilin-1-STAT3signaling and enhanced oxidative stress in hypertensive mice.Irbesartan treatment reduces vascular expression of Profilin-1and level of STAT3phosphorylation in hypertensive mice,contributing to improve vascular oxidative stress,and reduce blood pressure.

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