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罗格列酮对压力超负荷大鼠左心室肥厚和功能的影响
The Effects of Rosiglitazone on Pressure Overload-induced Left Ventricular Hypertrophy in Rats
【摘要】 目的:研究过氧化物酶体增殖物活化型受体γ(peroxisome proliferator-activated receptorγ,PPARγ)配体-罗格列酮对心肌肥厚的影响。方法:用腹主动脉缩窄法建立压力超负荷性心肌肥大大鼠模型。40只雄性大鼠,实验分4组(空白对照组、假手术组、手术组、手术+罗格列酮组),手术+罗格列酮组术后即用罗格列酮5mg/(kg.d)灌胃,持续16周,实验过程对血压、左心室功能等指标进行测定。结果:实验结束时手术组鼠尾血压、左心室重量/体重(LVMI)、左心室收缩末压(LVESP)和左心室舒张末压(LVEDP)均分别较假手术组增高(P<0.01),左心室压力上升最大速率(+dp/dtmax,P<0.05)和左心室压力下降最大速率(-dp/dtmax,P<0.01)较假手术组下降。罗格列酮治疗16周后与手术组比较血压、LVMI、LVEDP均下降(P<0.01),+dp/dtmax上升(P<0.05)。病理提示用罗格列酮后手术组心肌细胞肥厚改善。结论:PPARγ激动剂罗格列酮具有抑制大鼠左心室肥大的形成和改善左心室功能的作用,可能与其降低血压,调整肥厚心肌的代谢以及抑制血管紧张素Ⅱ、内皮素Ⅰ参与的心肌肥厚过程有关。
【Abstract】 Objective:To investigate the effects of a peroxisome proliferator-activated receptor γ(PPAR γ) activator,Rosiglitazone(RG),on left ventricular hypertrophy(LVH) in rats with pressure-overload cardiac hypertrophy.Methods: The LVH in rats was induced by partial occlusion of the abdominal aorta.Forty male rats were divided into four groups(Control,Sham,Operated,Operated+RG).The Operated + RG group was given ig RG 5 mg/(kg·d)for 16 weeks following surgery,and the other groups were treated with placebo by the same way.Body weight(BW),blood pressure,LV weight(LVW),LVW/BW and LV function were measured during the experiment.Results: Sixteen weeks later,compared with the Sham group,tail blood pressure(BP),LVW/BW,LV ending systolic pressure(LVESP),and LV ending diastolic pressure(LVEDP) increased respectively(P<0.01);the maximal values of positive rate of LV pressure(+dp/dtmax,P<0.05) and the maximal values of negative rate of LV pressure(-dp/dtmax,P<0.01) decreased in the Operated group. Compared with the Operated group,tail blood pressure,LVW/BW and LVEDP decreased(P<0.01);the LV +dp/dtmax increased(P<0.05) in the Operated+RG group.The histological assessment revealed that LVH in the Operated was improved by RG.Conclusion:RG as a PPAR γ agonist can inhibit development of LVH and improve LV function in rats with pressure-overload.It is likely to regulate the metabolism of LVH,decrease the blood pressure,and inhibit the angiotensinⅡand endothelin-I in the formation of LVH.
【Key words】 PPAR γ/agonist; pressure-overload; hypertrophy; left ventricular; heart function tests; rats;
- 【文献出处】 广州医学院学报 ,Academic Journal of Guangzhou Medical College , 编辑部邮箱 ,2006年04期
- 【分类号】R541
- 【被引频次】1
- 【下载频次】68