CAJ | 학술논문

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 Ang1-74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 mR-NA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。
목적：관찰혈관긴장소1-7（angiotensin 1-7，Ang 1-7）대작산거양피질동（deoxycorticosterone acetate，DOCA）염민감성고혈압대서적좌심실비후급심기섬유화적영향급기가능궤제。방법♂ SD 대서，행좌신절제술후피하주사DOCA，병음용1％록화납용액4주，건립DOCA-염형고혈압모형。재모형건립적동시，사용식입대서배부피하적Alzet미삼투빙만성관류 Ang1-74주，제량위200 ng · kg－1· min－1。대조조급여생리염수。측량대서적동맥혈압화좌심실공능，병재HE염색표본측량심기세포면적，재천랑성홍염색표본측량심기섬유화면적。Real-time PCR법검측대서심기조직적심방리납인자（ANF ）화β-기구단백중련（β-MHC）mRNA적표체，단백면역인적법관찰심기조직TGF-β1단백적표체변화。결과 DOCA염형대서재모형건립적제1주개시，출현동맥혈압적명현증가，재제4주말체봉치；동시기좌실수축말기압（LVESP）、좌실서장말기압（LVEDP）화심실수축시실내압최대상승속솔（＋dp／dt）야발생명현변화。만성관류Ang 1-7후DOCA염형대서적4주말적동맥혈압、LVESP화LVEDP균명현강저，이＋dp／dt명현증가（P＜0.05，n＝7）。Ang 1-7관류가이명현강저DOCA염형대서적심장지수화심기세포면적，이급상조적ANF화β-MHC mR-NA표체（P＜0.05，n ＝7）。동시，Ang 1-7야가명현강저 DOCA염형대서적혈관주위섬유화화간질섬유화면적，병명현억제DOCA염형대서증가적TGF-β1표체（P＜0.05，n＝7）。결론 Ang 1-7가이통과강저DOCA염형고혈압대서적동맥혈압화개선좌심실비후화심기섬유화，이발휘심장보호효응。
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.