Huangfu Weizhong, Chang Fuhou, Wang Minjie, Gao Ruiying
Department of Gerontology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
College of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
Pak J Pharm Sci. 2019 Sep;32(5(Special)):2495-2499.
Hypertension is a common cardiovascular disease in clinical scenario. The level of leptin changes with the development of hypertension and is regulated by Aldehyde dehydrogenase2 (ALDH2). Our study explored the relationship between irbesartan treatment and ALDH2. Spontaneously hypertensive rats were treated with irbesartan solution and ALDH2 over expression adenovirus vector for experimental group, and the equivalent amount of spontaneously hypertensive rats was treated with irbesartan solution and null adenovirus vector for control group. Sham group included spontaneously hypertensive rats treated with saline solution and null adenovirus vector. Pathological change of cardiac muscle tissue was observed with microscope. N-terminal Pro-brain natriuretic peptide, blood pressure, left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS) and renal function were assessed to determine cardiovascular function. Expression of serum leptin and mRNA of leptin were examined, respectively. ALDH2 was confirmed by western blot examination. Statistical Analysis was performed to determine correlation. Compared with sham group, ALDH2 were decreased significantly in control group. Remarkable pathological changes of cardiovascular and renal injury were observed in control group rats, including increased NT-proBNP, renal interstitial fibrosis and aberrant hypertension. Compared with control group, experimental group had lower levels of blood pressure and NT-proBNP, but higher level of Glomerular Filtration Rate (GFR). Moreover, irbesartan -treated rats had significantly higher levels of leptin, suggesting irbesartan treatment ameliorated symptoms of hypertension. Expression of serum leptin had a negative correlation with mRNA of leptin (P<0.05). Moreover, compared with control group, ALDH2 over expression significantly improved irbesartan treatment, verified by hypertension related index. Decreased ALDH2 expression were correlated with progression of hypertension. Rats with Hypertension indeed benefited from irbesartan treatment. ALDH2 elevated the drug susceptibility of irbesartan treatment for hypertension via regulating serum leptin, and improved efficacy of irbesartan treatment on hypertension.
高血压是临床常见的心血管疾病。瘦素水平随高血压的发展而变化,并受乙醛脱氢酶2(ALDH2)调节。我们的研究探讨了厄贝沙坦治疗与ALDH2之间的关系。将自发性高血压大鼠分为实验组,用厄贝沙坦溶液和ALDH2过表达腺病毒载体处理;等量的自发性高血压大鼠分为对照组,用厄贝沙坦溶液和空腺病毒载体处理。假手术组包括用生理盐水溶液和空腺病毒载体处理的自发性高血压大鼠。用显微镜观察心肌组织的病理变化。评估N末端脑钠肽前体、血压、左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)和肾功能以确定心血管功能。分别检测血清瘦素表达和瘦素mRNA。通过蛋白质免疫印迹法检测ALDH2。进行统计分析以确定相关性。与假手术组相比,对照组的ALDH2显著降低。对照组大鼠出现明显的心血管和肾损伤病理变化,包括NT-proBNP升高、肾间质纤维化和异常高血压。与对照组相比,实验组的血压和NT-proBNP水平较低,但肾小球滤过率(GFR)较高。此外,厄贝沙坦治疗的大鼠瘦素水平显著更高,提示厄贝沙坦治疗改善了高血压症状。血清瘦素表达与瘦素mRNA呈负相关(P<0.05)。此外,与对照组相比,ALDH2过表达显著改善了厄贝沙坦治疗效果,这通过高血压相关指标得到验证。ALDH2表达降低与高血压进展相关。高血压大鼠确实从厄贝沙坦治疗中获益。ALDH2通过调节血清瘦素提高了厄贝沙坦治疗高血压的药物敏感性,并改善了厄贝沙坦治疗高血压的疗效。