Abstract：
This study evaluated the effect of sacubtril/valsartan on cardiac remodeling, molecular and cellular adaptations in experimental (rat) model of hypertension-induced hypertrophic cardiomyopathy. Thirty Wistar Kyoto rats, 10 healthy (control) and 20 rats with confirmed hypertension-induced hypertrophic cardiomyopathy (HpCM), were used for this study. The HpCM group was further subdivided into untreated and sacubitril/valsartan-treated groups. Myocardial structure and function were assessed using echocardiography, Langendorff\'s isolated heart experiment, blood sampling and qualitative polymerase chain reaction. Echocardiographic examinations revealed protective effects of sacubitril/valsartan by improving left ventricular internal diameter in systole and diastole and fractional shortening. Additionally, sacubitril/valsartan treatment decreased systolic and diastolic blood pressures in comparison with untreated hypertensive rats. Moreover, sacubitril/valsartan treatment reduced oxidative stress and apoptosis (reduced expression of Bax and Cas9 genes) compared to untreated rats. There was a regular histomorphology of cardiomyocytes, interstitium, and blood vessels in treated rats compared to untreated HpCM rats which expressed hypertrophic cardiomyocytes, with polymorphic nuclei, prominent nucleoli and moderately dilated interstitium. In experimental model of hypertension-induced hypertrophic cardiomyopathy, sacubitril/valsartan treatment led to improved cardiac structure, haemodynamic performance, and reduced oxidative stress and apoptosis. Sacubitril/valsartan thus presents as a potential therapeutic strategy resulted in hypertension-induced hypertrophic cardiomyopathy.
摘要：
这项研究评估了sacubtril/缬沙坦对心脏重塑的影响，高血压诱发的肥厚型心肌病的实验（大鼠）模型中的分子和细胞适应。30只Wistar京都老鼠，10只健康（对照）和20只确诊为高血压性肥厚型心肌病（HpCM）的大鼠，用于这项研究。HpCM组进一步细分为未治疗和沙库巴曲/缬沙坦治疗组。使用超声心动图评估心肌结构和功能，Langendorff的孤立心脏实验,采血和定性聚合酶链反应。超声心动图检查显示，沙库巴曲/缬沙坦可改善收缩期和舒张期的左心室内径以及缩短期。此外,与未经治疗的高血压大鼠相比，沙库巴曲/缬沙坦治疗可降低收缩压和舒张压。此外，与未处理的大鼠相比,沙库巴曲/缬沙坦处理减少了氧化应激和细胞凋亡(Bax和Cas9基因的表达减少)。心肌细胞有规律的组织形态学，间质,与未处理的表达肥大心肌细胞的HpCM大鼠相比，具有多态核，突出的核仁和适度扩张的间质。在高血压诱发的肥厚型心肌病的实验模型中，沙库巴曲/缬沙坦治疗可改善心脏结构，血液动力学表现，并减少氧化应激和细胞凋亡。因此，沙库必曲/缬沙坦是导致高血压诱发的肥厚型心肌病的潜在治疗策略。
