血管紧张素1-7减弱醋酸去氧皮质酮盐型高血压大鼠的左心室重构

Angiotensin 1-7 attenuates left ventricular remodeling in deoxycorticosterone acetate salt hypertensive rats

目的观察血管紧张素1-7(angiotensin 1-7,Ang 1-7)对醋酸去氧皮质酮(deoxycorticosterone acetate,DOCA)盐敏感性高血压大鼠的左心室肥厚及心肌纤维化的影响及其可能机制。方法♂SD大鼠,行左肾切除术后皮下注射DOCA,并饮用1%氯化钠溶液4周,建立DOCA-盐型高血压模型。在模型建立的同时,使用植入大鼠背部皮下的Alzet微渗透泵慢性灌流Ang1-7 4周,剂量为200 ng·kg-1·min-1。对照组给予生理盐水。测量大鼠的动脉血压和左心室功能,并在HE染色标本测量心肌细胞面积,在天狼星红染色标本测量心肌纤维化面积。Real-time PCR法检测大鼠心肌组织的心房利钠因子(ANF)和β-肌球蛋白重链(β-MHC)mRNA的表达,蛋白免疫印迹法观察心肌组织TGF-β1蛋白的表达变化。结果 DOCA盐型大鼠在模型建立的第1周开始,出现动脉血压的明显增加,在第4周末达峰值;同时其左室收缩末期压(LVESP)、左室舒张末期压(LVEDP)和心室收缩时室内压最大上升速率(+dp/dt)也发生明显变化。慢性灌流Ang 1-7后DOCA盐型大鼠的4周末的动脉血压、LVESP和LVEDP均明显降低,而+dp/dt明显增加(P<0.05,n=7)。Ang 1-7灌流可以明显降低DOCA盐型大鼠的心脏指数和心肌细胞面积,以及上调的ANF和β-MHC mRNA表达(P<0.05,n=7)。同时,Ang 1-7也可明显降低DOCA盐型大鼠的血管周围纤维化和间质纤维化面积,并明显抑制DOCA盐型大鼠增加的TGF-β1表达(P<0.05,n=7)。结论 Ang 1-7可以通过降低DOCA盐型高血压大鼠的动脉血压和改善左心室肥厚和心肌纤维化,而发挥心脏保护效应。

Aim To investigate the effect of angioten-sin 1-7 （Ang 1-7 ）on the cardiac hypertrophy and my-ocardial fibrosis in deoxycorticosterone acetate （DOCA）-salt hypertensive rats and its possible mecha-nism.Methods Male Sprague-Dawley rats were used to establish DOCA-salt hypertensive model,which un-derwent uninephrectomy surgery and were subcutane-ously injected with a DOCA,and replaced drinking water with 1% saline solution for 4 weeks.DOCA-salt animals were implanted with osmotic minipumps, which delivered Ang 1-7 chronically for 4 weeks （200 ng ·kg-1 ·min-1 ）.Arterial blood pressure,left ven-tricular function in rats,the area of myocardial cells in HE stained specimens,and the area of myocardial fi-brosis Sirius red staining specimens were measured. Real time PCR was used to detect the expression of at-rial natriuretic factor （ANF ） and β-myosin heavy chain （β-MHC）mRNA in heart,and TGF-β1 protein expression was observed by Western blot in myocardial tissue.Results In the first week,DOCA salt rat had a significant increase in arterial blood pressure,and reached a peak in the fourth week;while the left ven-tricular end-systolic pressure （LVESP）,left ventricu-lar end-diastolic pressure （LVEDP ） and ventricular contraction the maximum rate of pressure rise （＋dp/dt）had also undergone significant changes in DOCA salt rats. After chronic infusion of Ang 1-7 for 4 weeks,the arterial pressure,LVESP and LVEDP were significantly reduced and ＋dp/dt were increased sig-nificantly in DOCA salt rats （P〈0.05 ,n=7 ）.Ang 1-7 significantly reduced the cardiac index and myocar-dial cell area,as well as the up-regulated expression of ANF and β-MHC mRNA in DOCA salt rats （P 〈0.05 ,n =7 ）.Meanwhile,Ang 1-7 also significantly decreased the perivascular fibrosis and interstitial fibro-sis area, and significantly inhibited the increase of TGF-β1 expression in DOCA salt rats （P〈0.05 ,n=7 ）.Conclusion These results indicate that Ang 1-7 has a cardioprotective effects through reducing arterial pressure and improving cardiac fibrosis and hypertro-phy in the DOCA-salt model of hypertension.