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川陈皮素可改善 2K-1C 高血压大鼠的左心室和肾脏变化。

Nobiletin resolves left ventricular and renal changes in 2K-1C hypertensive rats.

机构信息

Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.

Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.

出版信息

Sci Rep. 2022 Jun 3;12(1):9289. doi: 10.1038/s41598-022-13513-6.

DOI:10.1038/s41598-022-13513-6
PMID:35662276
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9166784/
Abstract

This study investigated the effects of nobiletin on cardiorenal changes and the underlying mechanisms involved in two-kidney, one-clip (2K-1C) hypertension. 2K-1C rats were treated with nobiletin (15 or 30 mg/kg/day) or losartan (10 mg/kg/day) for 4 weeks (n = 8/group). Nobiletin (30 mg/kg) reduced high levels of blood pressure and circulating angiotensin II and angiotensin-converting enzyme activity in 2K-1C rats. Left ventricular (LV) dysfunction and remodelling in 2K-1C rats were alleviated in the nobiletin-treated group (P < 0.05). Nobiletin reduced the upregulation of Ang II type I receptor (ATR)/JAK (Janus kinase)/STAT (signal transducer and activator of transcription) protein expression in cardiac tissue of 2K-1C rats (P < 0.05). The reduction in kidney function, and accumulation of renal fibrosis in 2K-1C rats were alleviated by nobiletin (P < 0.05). Overexpression of ATR and NADPH oxidase 4 (Nox4) protein in nonclipped kidney tissue was suppressed in the nobiletin-treated group (P < 0.05). The elevations in oxidative stress parameters and the reductions in antioxidant enzymes were attenuated in 2K-1C rats treated with nobiletin (P < 0.05). In summary, nobiletin had renin-angiotensin system inhibitory and antioxidant effects and attenuated LV dysfunction and remodelling via restoration of the ATR/JAK/STAT pathway. Nobiletin also resolved renal damage that was related to modulation of the ATR/Nox4 cascade in 2K-1C hypertension.

摘要

本研究探讨了川陈皮素对二肾一夹（2K-1C）高血压引起的心肾变化及相关机制的影响。2K-1C 大鼠给予川陈皮素（15 或 30mg/kg/天）或氯沙坦（10mg/kg/天）治疗 4 周（每组 n=8）。川陈皮素（30mg/kg）降低 2K-1C 大鼠血压和循环血管紧张素 II 和血管紧张素转换酶活性的高水平。川陈皮素治疗组减轻了 2K-1C 大鼠的左心室（LV）功能障碍和重构（P<0.05）。川陈皮素降低了 2K-1C 大鼠心脏组织中血管紧张素 II 型 1 受体（ATR）/JAK（Janus 激酶）/STAT（信号转导和转录激活因子）蛋白表达的上调（P<0.05）。川陈皮素减轻了 2K-1C 大鼠肾功能下降和肾纤维化堆积（P<0.05）。川陈皮素治疗组减轻了非夹闭侧肾脏组织中 ATR 和 NADPH 氧化酶 4（Nox4）蛋白的过表达（P<0.05）。川陈皮素治疗减轻了 2K-1C 大鼠氧化应激参数的升高和抗氧化酶的降低（P<0.05）。综上所述，川陈皮素具有肾素-血管紧张素系统抑制和抗氧化作用，通过恢复 ATR/JAK/STAT 通路减轻 LV 功能障碍和重构。川陈皮素还通过调节 2K-1C 高血压中的 ATR/Nox4 级联反应来解决与肾损伤相关的问题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243c/9166784/9cd5217f2b97/41598_2022_13513_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243c/9166784/4a29fa998b0f/41598_2022_13513_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243c/9166784/5adfc145f599/41598_2022_13513_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243c/9166784/d637a1914dd3/41598_2022_13513_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/243c/9166784/d7ed6b90737e/41598_2022_13513_Fig8_HTML.jpg
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