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压力负荷下缬沙坦对钙调神经磷酸酶介导心肌肥大通路的影响(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2003年第3期
页码:
215-217
栏目:
实验研究
出版日期:
2003-05-01

文章信息/Info

Title:
Effects of Valsartan on calcineurin-dependend signal pathway in pressure overload-induced cardiac hypertrophy in rat
作者:
周兴文李刚速晓华
成都军区成都总医院心血管内科,四川 成都610083
Author(s):
ZHOU Xing-wenLI GangSU Xiao-hua
Department of Cardiology,General Hospital of Cheng du Army,Cheng du,Si chuan 610083,China
关键词:
缬沙坦钙调神经磷酸酶信号通路活化T细胞核因子血管紧张素Ⅱ
Keywords:
Valsartancalcineurinsignal pathwayNFAT3angiotensionⅡ
分类号:
R542.2
DOI:
-
文献标识码:
A
摘要:
目的:探讨压力超负荷模型下血管紧张素Ⅱ(AngⅡ)受体拮抗剂缬沙坦对钙调神经磷酸酶(CaN)介导心肌肥大通路的影响及AngⅡ的致心肌肥厚作用。方法:腹主动脉缩窄法建立大鼠压力超负荷模型,放射免疫法检测血浆、心肌AngⅡ浓度,WesternBlot检测心肌CaN,活化T细胞核因子(NFAT3)蛋白表达,发色底物法检测CaN比活性,并测定左室重量指数。结果:缬沙坦组血浆AngⅡ浓度高于对照组(P<0.05),心肌AngⅡ浓度则相反(P<0.05),缬沙坦组CaN表达及活性低于对照组(P<0.01),NFAT3表达低于对照组(P<0.05),两组各项指标与假手术组相比均差异显著。结论:AngⅡ参与激活压力负荷下钙调神经磷酸酶通路,缬沙坦间接干预钙调神经磷酸酶介导通路并抑制心肌肥厚的形成。
Abstract:
AIM:To determine the effects of Valsartan on calcineurin-dependend signal pathway and evaluate the role of AngⅡ in cardiac pressure-overload hypertrophy.METHODS:The model of pressure overload was established by abdominal arota constriction.30 male Wistar rats randomized into three groups,sham-operated group,banding group,banding and Valsartan administration group.Two weeks later,Radioimmunoassays measured AngⅡ levels in blood and left ventricular.Western blot measured CaN and NFAT3 protein content and phosphatase assay measured CaN activity.RESULTS:AngⅡ concentration levels of Valsartan group in myocardia was lower than that of banding group(P<0.05),otherwise in blood(P<0.05).The protein content of CaN and enzyme activity of CaN in banding group were higher than those in Valsartan group significantly (P<0.01),meanwhile,the protein content of NFAT3 in banding group higher than it in Valsartan group too(P<0.05).The heart /body weight ratio of banding group was higher than Valsartan group.CONCLUSION:AngⅡ involve in promoting the activity of calcineurin-dependend signal pathway in pressure overload model

参考文献/References

[1] Molkentin JD,Lu JR,Antos CL,et al.A calcineurin-dependent transcriptional pathway for cardiac hypetrophy[J].Cell,1998, 93(17):215-218.

[2]Lee MA,Bohm M,Paul M,et al.Tissue renin-angiotension system:Their role in cardiovascular disease [J]. Circ Res,1993,87:7-14.

[3] Ohkusa T,Hisamotsu Y,Yano M,et al.Altered cardiac mechanism and sarcoplasmicreticulum function in pressure overload-induced cardiac hypertrophy in rats[J].J Mol Cell Cardiol,1997,29:45-54.

[4]符民桂,唐朝枢.钙调神经磷酸酶活性测定[J].中国动脉硬化杂志,2000,8(1):79-80.

[5] Lim HW, De Windt LJ,Steinberg L, et al. Calcineurin expression, activation, and function in cardiac pressure overload hypertrophy[J]. Circulation, 2000,101:2431-2437.

[6] Sugden PH. Signaling in myocardial hypertrophy:life after calcineurin?[J].CircRes,1999,84:633-646.

备注/Memo

备注/Memo:
收稿日期:2002-12-28.
更新日期/Last Update: 2003-05-01