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雄性 Wistar 大鼠随年龄增长发生高血压的发展和恶化:原花青素对高血压的纠正作用。

Development and Worsening of Hypertension with Age in Male Wistar Rats as a Physiological Model of Age-Related Hypertension: Correction of Hypertension with Taxifolin.

机构信息

Biological Testing Laboratory, Shemyakin-Ovchinnicov Institute of Bioorganic Chemistry (Branch), Russian Academy of Sciences, Prospekt Nauki, 6, Pushchino 142290, Russia.

出版信息

Int J Mol Sci. 2024 Oct 18;25(20):11216. doi: 10.3390/ijms252011216.

Abstract

To preclinically study the effectiveness of new antihypertensive drugs, various animal hypertension models are used. However, most of them do not correspond to primary hypertension, which develops in people with age. We used male Wistar rats of 4, 10, 12 and 18 months old. The animals were divided according to systolic blood pressure (SBP) into normotensive (SBP ≤ 114 mmHg) or hypertensive (SBP ≥ 115 mmHg). Within hypertensive animals, two cohorts were distinguished-with SBP below and above 125 mmHg. The animals received 100 µg/kg of taxifolin intraperitoneally for 7 days. A significant difference was shown between animals with SBP above and below 115 mmHg, as well as between cohorts of hypertensive animals with SBP above and below 125 mmHg within each age. The number of animals with elevated SBP increased with age both for clusters with an SBP above 115 mmHg and for cohorts with an SBP above 125 mmHg. Administration of taxifolin led to a significant decrease in the SBP only in hypertensive animals. A physiological model of age-related hypertension was obtained in male Wistar rats. It has been shown that hypertension develops and worsens with age. In preclinical studies, it should be taken into account that drugs may have different effects depending on the initial SBP of the animals.

摘要

为了在临床前研究新型抗高血压药物的疗效,我们使用了各种动物高血压模型。然而,这些模型大多数与原发性高血压不符,原发性高血压是在年龄增长的人群中发展起来的。我们使用了 4 个月、10 个月、12 个月和 18 个月大的雄性 Wistar 大鼠。根据收缩压(SBP),动物被分为正常血压(SBP≤114mmHg)或高血压(SBP≥115mmHg)。在高血压动物中,根据 SBP 分为低于和高于 125mmHg 的两个亚组。动物接受Taxifolin 100µg/kg 腹腔内注射,持续 7 天。结果显示,SBP 高于和低于 115mmHg 的动物之间,以及每个年龄组中 SBP 高于和低于 125mmHg 的高血压动物亚组之间均存在显著差异。随着年龄的增长,SBP 升高的动物数量在 SBP 高于 115mmHg 的亚组和 SBP 高于 125mmHg 的亚组中均有所增加。Taxifolin 的给药仅在高血压动物中显著降低 SBP。我们在雄性 Wistar 大鼠中获得了一种与年龄相关的高血压生理模型。结果表明,高血压随着年龄的增长而发展和恶化。在临床前研究中,应考虑到药物可能会根据动物的初始 SBP 产生不同的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0afb/11509042/d38e019102be/ijms-25-11216-g001.jpg

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