N. A. Papiashvili, M. V. Ghonghadze, N. V. Sharikadze, M. P. Khutsishvili, K. A. Bakuridze, A. J. Bakuridze, N. V. Gongadze, G. V. Sukoyan
{"title":"黄酮类芹菜素对实验性肾性高血压血流动力学指标、压力反射功能、心脏和肾脏重塑及血管活性炎症生物标志物的影响","authors":"N. A. Papiashvili, M. V. Ghonghadze, N. V. Sharikadze, M. P. Khutsishvili, K. A. Bakuridze, A. J. Bakuridze, N. V. Gongadze, G. V. Sukoyan","doi":"10.13005/bpj/2760","DOIUrl":null,"url":null,"abstract":"The hypothesis stated here that, the long-term prevention by natural flavonoid phenolic compound, for example apigenin (Apg), improves baroreflex sensitivity and vascular resistance and occurs beneficial action for attenuation the renal hypertension (RH). One-kidney, 1-clip rats (1K1C) were treated with Apg for 2 weeks after 1 week of surgical intervention. At the end of the study in the control RH group the blood pressure (BP) increased on average by 43.5%, decreased in heart period (HP) by 9.8%, cardiochronotropic (vagal) component of baroreflex sensitivity (BRS) by 50%, and adrenergic component by 34%. Thus, in 1K1C experimental model of hypertension, provides switching to parasympathetic component and accompanied with proportionally nearly two-fold increase in epinephrine (EPN) and norepinephrine (NE) without changes in EPN/NE ratio. Morphometric changes in the kidney and heart confirmed the development of kidney and cardiac hypertrophy and renal functioning disturbances (blood urea nitrogen (BUN) increased in more than two-fold) and markers of sodium reabsorption in proximal tubule, total trans-EETs, decreased in 1.6-fold. The pronounced increased proinflammatory cytokines, interleukin 1b (IL1 b), endothelin -1 (ET-1) and tumor necrosis factor (TNF)-a confirmed the formation of “sterile inflammation” which strengthening by the nearly two-fold decreasing in the level of anti-inflammatory (vasodilatory) mediators, prostaglandin E2 (PGE2). Preventive long-term regime treatment with Apg (5mg/kg i.p./daily) in RH rats significantly decreased BP by 18.6%, increased parasympathetic component of BRS by 38.5% without marked altered its sympathetic component. Such deremodeling in BRS sensitivity associated with significant decreased in heart and kidney hypertrophy and functional activity of kidney, normalization of BUN and total EETs, reducing in circulating plasma level of catecholamines, and markedly attenuated progression of inflammation, decreased of proinflammatory levels of cytokines. 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引用次数: 0
摘要
本研究假设,芹菜素(Apg)等天然类黄酮酚类化合物的长期预防可以改善压力反射敏感性和血管阻力,对降低肾性高血压(RH)有有益作用。单肾一夹大鼠(1K1C)在手术干预1周后用Apg治疗2周。在研究结束时,对照组的血压(BP)平均上升43.5%,心期(HP)下降9.8%,压力反射敏感性(BRS)的促心性(迷走神经)成分下降50%,肾上腺素能成分下降34%。因此,在1K1C高血压实验模型中,提供向副交感神经成分的转换,并伴随着肾上腺素(EPN)和去甲肾上腺素(NE)按比例增加近两倍,而EPN/NE比值没有变化。肾脏和心脏的形态变化证实了肾脏和心脏肥厚的发展以及肾功能障碍(血尿素氮(BUN)增加了两倍以上),近端小管钠重吸收标志物,总反式eets减少了1.6倍。促炎因子,白细胞介素1b (il - 1b)、内皮素-1 (ET-1)和肿瘤坏死因子(TNF) -1的显著增加证实了“无菌炎症”的形成,这种炎症通过抗炎(血管扩张)介质前列腺素E2 (PGE2)水平的近两倍下降而加强。RH大鼠预防性长期用药Apg (5mg/kg i.p./daily)可显著降低血压18.6%,增加BRS副交感神经成分38.5%,但交感神经成分无明显改变。这种BRS敏感性的重塑与心脏和肾脏肥厚和肾脏功能活性的显著降低、BUN和总eet的正常化、循环血浆儿茶酚胺水平的降低、炎症进展的显著减轻、促炎细胞因子水平的降低相关。因此,Apg通过发挥抗高血压、心脏和肾保护作用以及衰减“无菌炎症”,在RH大鼠中提供了预防性有益的多能性作用。
Efficacy of Flavonoid Apigenin on Hemodynamic indices, Baroreflex Function, Cardiac and Kidney Remodeling and Vasoactive-Inflammatory Biomarkers in Experimental Renal Hypertension
The hypothesis stated here that, the long-term prevention by natural flavonoid phenolic compound, for example apigenin (Apg), improves baroreflex sensitivity and vascular resistance and occurs beneficial action for attenuation the renal hypertension (RH). One-kidney, 1-clip rats (1K1C) were treated with Apg for 2 weeks after 1 week of surgical intervention. At the end of the study in the control RH group the blood pressure (BP) increased on average by 43.5%, decreased in heart period (HP) by 9.8%, cardiochronotropic (vagal) component of baroreflex sensitivity (BRS) by 50%, and adrenergic component by 34%. Thus, in 1K1C experimental model of hypertension, provides switching to parasympathetic component and accompanied with proportionally nearly two-fold increase in epinephrine (EPN) and norepinephrine (NE) without changes in EPN/NE ratio. Morphometric changes in the kidney and heart confirmed the development of kidney and cardiac hypertrophy and renal functioning disturbances (blood urea nitrogen (BUN) increased in more than two-fold) and markers of sodium reabsorption in proximal tubule, total trans-EETs, decreased in 1.6-fold. The pronounced increased proinflammatory cytokines, interleukin 1b (IL1 b), endothelin -1 (ET-1) and tumor necrosis factor (TNF)-a confirmed the formation of “sterile inflammation” which strengthening by the nearly two-fold decreasing in the level of anti-inflammatory (vasodilatory) mediators, prostaglandin E2 (PGE2). Preventive long-term regime treatment with Apg (5mg/kg i.p./daily) in RH rats significantly decreased BP by 18.6%, increased parasympathetic component of BRS by 38.5% without marked altered its sympathetic component. Such deremodeling in BRS sensitivity associated with significant decreased in heart and kidney hypertrophy and functional activity of kidney, normalization of BUN and total EETs, reducing in circulating plasma level of catecholamines, and markedly attenuated progression of inflammation, decreased of proinflammatory levels of cytokines. Thus, Apg provides preventive beneficial pluripotent action in RH rats by exerting antihypertensive, cardio- and renoprotective effects and attenuation of “sterile inflammation”.
期刊介绍:
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