替米沙坦对肾性高血压大鼠心肌Calsarcin-1、主动脉AT受体及外周血管生成素2的作用
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摘要
目的:研究肾血管性高血压大鼠心肌组织Calsarcin-1、主动脉AT1受体(AT1R)、AT2受体(AT2R)及外周血管生成素-2(angiopoietin-2)、血管紧张素Ⅱ(AngⅡ)表达水平的变化及替米沙坦的干预作用。
方法:清洁级雄性SD大鼠40只,随机分为对照组(n=8)、假手术组(n=8)、两肾一夹(two-kidney one clip,2K1C)组(n=12)和2K1C+替米沙坦组(n=12),2K1C组及2K1C+替米沙坦组采用2K1C方法制备高血压模型,其中,2K1C+替米沙坦组每天以替米沙坦(10mg/kg.d)灌胃干预,2K1C组采用等量蒸馏水灌胃。分别于术前及术后经动脉插管测血压,8周时以超声心动图检测心脏结构及功能变化,随后处死大鼠,取外周动脉血清以ELISA方法检测Ang-2及AngⅡ水平。取大鼠心脏及主动脉,用Western blotting法检测不同时期心肌组织Calsarcin-1、主动脉AT1R、AT2R蛋白表达水平。
结果:①与对照组、假手术组相比,2K1C组血压显著升高、心肌肥厚明显(P <0.01);2K1C+替米沙坦组血压较2K1C组明显降低,心肌肥厚亦明显减轻(P <0.01);②与对照组、假手术组相比,2K1C组动脉血清Ang-2水平明显升高(P <0.01),且与血压水平、心肌肥厚程度呈正相关;2K1C+替米沙坦组Ang-2水平与2K1C组差异无统计学意义(P >0.05),2K1C组及2K1C+替米沙坦组血清AngⅡ水平均升高(分别为P <0.05及P <0.01);③与对照组及假手术组相比,2K1C术后心肌Calsarcin-1表达水平明显下降(P <0.01),替米沙坦灌胃后,心肌中Calsarcin-1表达水平较未灌胃组升高(P <0.05);④与对照组、假手术组相比,2K1C组主动脉AT1R表达增加(P <0.05),AT2R无明显变化;替米沙坦干预后,AT1R、AT2R表达水平较2K1C组增加(P <0.05),且AT2R较AT1R增加明显。
结论:①肾血管性高血压大鼠外周动脉血清中血管生成素-2水平增加,且与心肌肥厚相关;替米沙坦可显著降低肾血管性高血压大鼠的血压、抑制心肌肥厚,对外周动脉血清血管生成素-2水平无明显影响,提示替米沙坦降压机制可能与Ang-2无关;②Calsarcin-1表达下调参与了高血压心肌肥厚的发生发展;替米沙坦可有效降压、上调Calsarcin-1表达水平,这可能是其逆转心肌肥厚的机制之一;③替米沙坦可上调主动脉AT2R表达水平,且与血压下降相关。
Objective To explore the changes of myocardial calsarcin-1 level , arterial angiotensinⅡreceptors level, plasma angiopoietin-2 and Ang-II level in different stages of cardiac hypertrophy by renovascular hypertensive (two-kidneys, oneclip, 2K1C) rat models, and the effects of telmisartan.
Methods 24 Male Sprague-Dawly rats were randomly divided into control group (n=8), sham operation group (n=8), 2 kidney 1 clip (2K1C) group (n=12) and 2K1C+telmisartan group(n=12). 2K1C hypertensive model was established in Sprague-Dawly rats by chronic partial occlusion of left renal artery. Before and after eight weeks of the operation, blood pressure were tested by arterial catheterization, the myocardial structure and function were obtained by ultrasonography, and the serum angiopoietin-2 and Ang-II were evaluated by ELISA, calsarcin-1 expression level in myocardium and AT1R, AT2R expression level in aorta were compared by western blotting.
Results①Eight weeks later, the blood pressure and the thickness of left ventricle in 2K1C group were significantly higher than that of control group and sham group (P<0.01). Compared with 2K1C group, the blood pressure and the the thickness of left ventricle were significantly decreased in 2K1C+ telmisartan group(P<0.01).②The serum level of angiopoietin-2 was markedly increased in 2K1C group, and was closely related to the blood pressure and the extent of myocardial hypertrophy, but was not decreased in 2K1C+telmisartan group(P>0.05). The AngⅡlevel in 2K1C group and telmisartan group were both increased (P<0.05 and P<0.01 respectively).③Compared with sham group, the calsarcin-1 level was markedly increased in 2K1C group(P<0.01), and after being treated for 8weeks, the calsarcin-1 level was higher than which of untreated group(P<0.05).④The AT1R level was markedly increased in 2K1C group(P<0.05), but AT2R was not increased(P>0.05),Compared with 2K1C group,AT1R,AT2R were both increased in telmisartan group(P>0.05).
Conclusions①Serum level of Angiopoietin-2 is increased in the renovascular hypertensive rats, and is related to myocardial hypertrophy. Telmisartan can reduce blood pressure and prevent myocardial hypertrophy, but can not decreased the angiopoietin-2 level, which indicate that telmisartan prevent myocardial hypertrophy maybe not associated with angiopoietin-2 level.②The decreased myocardiac calsarcin-1 level occurs in the early stage of cardiac hypertrophy and participates in its development, Telmisartan may increase calsarcin-1 level, which maybe one of mechanisms reversing cardiac hypertrophy by telmisartan.③Telmisartan can increase AT2R level, which is related to blood pressure.
方法:清洁级雄性SD大鼠40只,随机分为对照组(n=8)、假手术组(n=8)、两肾一夹(two-kidney one clip,2K1C)组(n=12)和2K1C+替米沙坦组(n=12),2K1C组及2K1C+替米沙坦组采用2K1C方法制备高血压模型,其中,2K1C+替米沙坦组每天以替米沙坦(10mg/kg.d)灌胃干预,2K1C组采用等量蒸馏水灌胃。分别于术前及术后经动脉插管测血压,8周时以超声心动图检测心脏结构及功能变化,随后处死大鼠,取外周动脉血清以ELISA方法检测Ang-2及AngⅡ水平。取大鼠心脏及主动脉,用Western blotting法检测不同时期心肌组织Calsarcin-1、主动脉AT1R、AT2R蛋白表达水平。
结果:①与对照组、假手术组相比,2K1C组血压显著升高、心肌肥厚明显(P <0.01);2K1C+替米沙坦组血压较2K1C组明显降低,心肌肥厚亦明显减轻(P <0.01);②与对照组、假手术组相比,2K1C组动脉血清Ang-2水平明显升高(P <0.01),且与血压水平、心肌肥厚程度呈正相关;2K1C+替米沙坦组Ang-2水平与2K1C组差异无统计学意义(P >0.05),2K1C组及2K1C+替米沙坦组血清AngⅡ水平均升高(分别为P <0.05及P <0.01);③与对照组及假手术组相比,2K1C术后心肌Calsarcin-1表达水平明显下降(P <0.01),替米沙坦灌胃后,心肌中Calsarcin-1表达水平较未灌胃组升高(P <0.05);④与对照组、假手术组相比,2K1C组主动脉AT1R表达增加(P <0.05),AT2R无明显变化;替米沙坦干预后,AT1R、AT2R表达水平较2K1C组增加(P <0.05),且AT2R较AT1R增加明显。
结论:①肾血管性高血压大鼠外周动脉血清中血管生成素-2水平增加,且与心肌肥厚相关;替米沙坦可显著降低肾血管性高血压大鼠的血压、抑制心肌肥厚,对外周动脉血清血管生成素-2水平无明显影响,提示替米沙坦降压机制可能与Ang-2无关;②Calsarcin-1表达下调参与了高血压心肌肥厚的发生发展;替米沙坦可有效降压、上调Calsarcin-1表达水平,这可能是其逆转心肌肥厚的机制之一;③替米沙坦可上调主动脉AT2R表达水平,且与血压下降相关。
Objective To explore the changes of myocardial calsarcin-1 level , arterial angiotensinⅡreceptors level, plasma angiopoietin-2 and Ang-II level in different stages of cardiac hypertrophy by renovascular hypertensive (two-kidneys, oneclip, 2K1C) rat models, and the effects of telmisartan.
Methods 24 Male Sprague-Dawly rats were randomly divided into control group (n=8), sham operation group (n=8), 2 kidney 1 clip (2K1C) group (n=12) and 2K1C+telmisartan group(n=12). 2K1C hypertensive model was established in Sprague-Dawly rats by chronic partial occlusion of left renal artery. Before and after eight weeks of the operation, blood pressure were tested by arterial catheterization, the myocardial structure and function were obtained by ultrasonography, and the serum angiopoietin-2 and Ang-II were evaluated by ELISA, calsarcin-1 expression level in myocardium and AT1R, AT2R expression level in aorta were compared by western blotting.
Results①Eight weeks later, the blood pressure and the thickness of left ventricle in 2K1C group were significantly higher than that of control group and sham group (P<0.01). Compared with 2K1C group, the blood pressure and the the thickness of left ventricle were significantly decreased in 2K1C+ telmisartan group(P<0.01).②The serum level of angiopoietin-2 was markedly increased in 2K1C group, and was closely related to the blood pressure and the extent of myocardial hypertrophy, but was not decreased in 2K1C+telmisartan group(P>0.05). The AngⅡlevel in 2K1C group and telmisartan group were both increased (P<0.05 and P<0.01 respectively).③Compared with sham group, the calsarcin-1 level was markedly increased in 2K1C group(P<0.01), and after being treated for 8weeks, the calsarcin-1 level was higher than which of untreated group(P<0.05).④The AT1R level was markedly increased in 2K1C group(P<0.05), but AT2R was not increased(P>0.05),Compared with 2K1C group,AT1R,AT2R were both increased in telmisartan group(P>0.05).
Conclusions①Serum level of Angiopoietin-2 is increased in the renovascular hypertensive rats, and is related to myocardial hypertrophy. Telmisartan can reduce blood pressure and prevent myocardial hypertrophy, but can not decreased the angiopoietin-2 level, which indicate that telmisartan prevent myocardial hypertrophy maybe not associated with angiopoietin-2 level.②The decreased myocardiac calsarcin-1 level occurs in the early stage of cardiac hypertrophy and participates in its development, Telmisartan may increase calsarcin-1 level, which maybe one of mechanisms reversing cardiac hypertrophy by telmisartan.③Telmisartan can increase AT2R level, which is related to blood pressure.
引文
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