Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Faculty of Medicine, Mahasarakham University, Maha Sarakham 44000, Thailand.
Biomed Pharmacother. 2022 Feb;146:112601. doi: 10.1016/j.biopha.2021.112601. Epub 2022 Jan 4.
Genistein is a bioflavonoid mainly found in soybean. This study evaluated the effect of genistein on vascular dysfunction and kidney damage in two-kidney, one-clipped (2K1C) hypertensive rats. Male Sprague-Dawley-2K1C hypertensive rats were treated with genistein (40 or 80 mg/kg) or losartan 10 mg/kg (n = 8/group). Genistein reduced blood pressure, attenuated the increase in sympathetic nerve-mediated contractile response and endothelial dysfunction in the mesenteric vascular beds and aorta of 2K1C rats. Increases in the intensity of tyrosine hydroxylase (TH) in the mesentery and plasma norepinephrine (NE) were alleviated in the genistein-treated group. Genistein also improved renal dysfunction, hypertrophy of the non-clipped kidney (NCK) and atrophy of the clipped kidney (CK) in 2K1C rats. Upregulation of angiotensin II receptor type I (ATR), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit 4 (Nox4) and Bcl2-associated X protein (BAX) and downregulation of B-cell lymphoma 2 (Bcl2) protein found in CK were restored by genistein. It also suppressed the overexpression of ATR, transforming growth factor beta I (TGF-β1), smad2/3 and p-smad3 in NCK. Genistein reduced serum angiotensin converting enzyme (ACE) activity and plasma angiotensin II (Ang II) in 2K1C rats. Low levels of catalase activity as well as high levels of superoxide generation and malondialdehyde (MDA) in 2K1C rats were restored by genistein treatment. In conclusion, genistein suppressed renin-angiotensin system-mediated sympathetic activation and oxidative stress in 2K1C rats. It alleviated renal atrophy in CK via modulation of ATR/NADPH oxidase/Bcl-2/BAX pathways and hypertrophy in NCK via ATR/TGF-β1/smad-dependent signalling pathways.
染料木黄酮是一种主要存在于大豆中的生物类黄酮。本研究评估了染料木黄酮对双肾一夹（2K1C）高血压大鼠血管功能障碍和肾脏损伤的影响。雄性 Sprague-Dawley-2K1C 高血压大鼠用染料木黄酮（40 或 80mg/kg）或氯沙坦 10mg/kg 治疗（每组 8 只）。染料木黄酮降低了血压，减轻了 2K1C 大鼠肠系膜血管床和主动脉中交感神经介导的收缩反应和内皮功能障碍的增加。染料木黄酮治疗组减轻了肠系膜酪氨酸羟化酶（TH）强度和血浆去甲肾上腺素（NE）的增加。染料木黄酮还改善了 2K1C 大鼠的肾功能障碍、未夹闭肾脏（NCK）肥大和夹闭肾脏（CK）萎缩。在 CK 中发现的血管紧张素 II 受体 1 型（ATR）、烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶亚基 4（Nox4）和 Bcl2 相关 X 蛋白（BAX）的上调以及 B 细胞淋巴瘤 2（Bcl2）蛋白的下调被染料木黄酮所恢复。它还抑制了 NCK 中 ATR、转化生长因子β I（TGF-β1）、smad2/3 和 p-smad3 的过度表达。染料木黄酮降低了 2K1C 大鼠的血清血管紧张素转换酶（ACE）活性和血浆血管紧张素 II（Ang II）。染料木黄酮治疗恢复了 2K1C 大鼠血清过氧化氢酶活性降低和超氧化物生成及丙二醛（MDA）水平升高。综上所述，染料木黄酮抑制了 2K1C 大鼠肾素-血管紧张素系统介导的交感神经激活和氧化应激。它通过调节 ATR/NADPH 氧化酶/Bcl-2/BAX 途径缓解 CK 中的肾脏萎缩，并通过 ATR/TGF-β1/smad 依赖性信号通路缓解 NCK 中的肾脏肥大。
