Department of Nephrology, The Second Affiliated Hospital of Third Military Medical University, Chongqing, 400037, China.
Department of Neurology and Neurosurgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, China.
Inflammopharmacology. 2018 Feb;26(1):119-132. doi: 10.1007/s10787-017-0394-4. Epub 2017 Sep 4.
Chronic kidney disease (CKD) is a significant global health concern with limited treatment options. Oxidative stress and inflammatory responses have been implicated in the pathology of CKD. Patients with CKD are frequently affected with neurological complications that affect both the central and peripheral nervous system. Identification of effective treatment strategies are of much clinical value in the therapy of CKD. Tangeretin, a plant-derived flavonoid has been described to retain extensive pharmacological properties. In the present study, we explored whether tangeretin exerted protective effects in 5/6 nephrectomized rats. CKD was induced in Sprague-Dawley rats by 5/6 nephrectomy (Nx). Separate groups of 5/6 Nx rats were treated with tangeretin (50, 100 or 200 mg/kg b.wt.) or enalapril for 30 days (starting 5 days after surgery for 35 days). Control animals were not subjected to Nx nor were treated with tangeretin or enalapril. Renal dysfunction, as evinced by raised serum urea, serum creatinine, proteinuria, and histological alterations were significantly reduced by tangeretin and enalapril treatment. 5/6 Nx animals exhibited raised levels of malondialdehyde (MDA) and reactive oxygen species. Elevated TNF-α, nitric oxide (NO) and cytokines-IL-6 and IL-1β with upregulated NF-κB/TNF-α/iNOS signalling pathways were effectively down-regulated by tangeretin. Cognitive disturbances and memory impairments observed in Nx rats were substantially improved by tangeretin. Collectively, the experimental data indicate that the anti-oxidant and anti-inflammatory effects of tangeretin effectively improved renal function and reduced the cognitive and memory impairments in CKD-induced animals.
慢性肾脏病（CKD）是一个重大的全球健康问题，其治疗选择有限。氧化应激和炎症反应与 CKD 的病理学有关。CKD 患者常伴有影响中枢和外周神经系统的神经并发症。确定有效的治疗策略在 CKD 的治疗中具有重要的临床价值。桔皮素是一种植物衍生的类黄酮，具有广泛的药理学特性。在本研究中，我们探讨了桔皮素是否对 5/6 肾切除大鼠发挥保护作用。通过 5/6 肾切除术（Nx）在 Sprague-Dawley 大鼠中诱导 CKD。将单独的 5/6 Nx 大鼠组用桔皮素（50、100 或 200mg/kg 体重）或依那普利治疗 30 天（从手术后 5 天开始 35 天）。对照动物未进行 Nx 处理，也未用桔皮素或依那普利处理。桔皮素和依那普利治疗显著降低了肾功能障碍，表现为血清尿素、血清肌酐、蛋白尿升高和组织学改变。5/6 Nx 动物表现出丙二醛（MDA）和活性氧水平升高。升高的 TNF-α、一氧化氮（NO）和细胞因子-IL-6 和 IL-1β以及上调的 NF-κB/TNF-α/iNOS 信号通路被桔皮素有效下调。在 Nx 大鼠中观察到的认知障碍和记忆损伤得到了明显改善。总的来说，实验数据表明，桔皮素的抗氧化和抗炎作用有效改善了肾功能，减少了 CKD 诱导动物的认知和记忆损伤。
