Rathi Vaishnavi, Sagi Sarada S K
Defence Institute of Physiology and Allied Sciences, DRDO, Delhi, India.
J Tradit Complement Med. 2024 Jun 28;15(5):482-494. doi: 10.1016/j.jtcme.2024.06.008. eCollection 2025 Sep.
The objective of the present study is to decipher the role of NF-κB and its associated downstream genes involved in causing inflammation in kidneys of rats under acute hypobaric hypoxia exposure. The study also aims at finding out the efficacy of quercetin in comparison with dexamethasone in prevention of hypobaric hypoxia induced renal inflammation. Sprague Dawley (SD) rats (n = 6) were preconditioned with 50 mg/Kg BW of quercetin, 1 h prior to hypobaric hypoxia exposure (12 h). The results revealed a significant increase in reactive oxygen species (ROS) generation and malondialdehyde (MDA) ( < 0.001) levels along with down regulation of GPx and SOD levels in kidney tissue of hypobaric hypoxia exposed rats as compared to control. However, ROS production and MDA levels in kidney tissues were reduced significantly ( < 0.001) with enhanced antioxidant enzyme levels (GPx and SOD) in rats fed with quercetin as compared to hypobaric hypoxia exposed control ( < 0.001). Protein expression analysis through western blotting and EMSA performed in nuclear extracts of kidneys, exhibited a significant upregulation of NF-κB under hypobaric hypoxic stress as compared to control. Whereas pretreatment with quercetin aids in downregulation of NF-κB expression in kidneys of rats as compared to the hypobaric hypoxia exposed group. Further, quercetin prophylaxis significantly reduced the expression of pro-inflammatory cytokines (TNF-α, IL-2 and IL-6), increased the anti-inflammatory cytokines (IL-10, IL-4 and TGF-β) along with reduced expression of cell adhesion molecules (ICAM-1, VCAM-1, E-selectin and P-selectin) in kidneys of rats under hypobaric hypoxia as compared to hypobaric hypoxia control. However, pre-treatment with dexamethasone was not as effective as quercetin, in controlling the renal inflammation. Furthermore, improved hematological parameters such as WBC, RBC, and platelet count indicated that quercetin is a well-functioning effective molecule under hypobaric hypoxic exposure. The histopathological and TEM findings, manifested the structural changes in tubular arrangements in kidneys of rats, and these changes were found to be modified by quercetin prophylaxis under hypobaric hypoxic stress. Hence, the present study indicates that, quercetin can be considered as a potential phytochemical flavonoid moiety in preventing the acute renal inflammation under hypobaric hypoxia.
本研究的目的是解读核因子-κB（NF-κB）及其相关下游基因在急性低压缺氧暴露下大鼠肾脏炎症发生过程中的作用。该研究还旨在探究槲皮素与地塞米松相比，在预防低压缺氧诱导的肾脏炎症方面的效果。将6只斯普拉格-道利（SD）大鼠，在低压缺氧暴露（12小时）前1小时，用50mg/Kg体重的槲皮素进行预处理。结果显示，与对照组相比，低压缺氧暴露大鼠肾组织中活性氧（ROS）生成和丙二醛（MDA）水平显著升高（P<0.001），同时谷胱甘肽过氧化物酶（GPx）和超氧化物歧化酶（SOD）水平下调。然而，与低压缺氧暴露对照组相比，喂食槲皮素的大鼠肾组织中ROS生成和MDA水平显著降低（P<0.001），抗氧化酶水平（GPx和SOD）升高（P<0.001）。通过对肾脏核提取物进行蛋白质印迹和电泳迁移率变动分析（EMSA）的蛋白质表达分析显示，与对照组相比，低压缺氧应激下NF-κB显著上调。而与低压缺氧暴露组相比，槲皮素预处理有助于下调大鼠肾脏中NF-κB的表达。此外，与低压缺氧对照组相比，槲皮素预防显著降低了低压缺氧大鼠肾脏中促炎细胞因子（肿瘤坏死因子-α、白细胞介素-2和白细胞介素-6）的表达，增加了抗炎细胞因子（白细胞介素-10、白细胞介素-4和转化生长因子-β）的表达，同时降低了细胞黏附分子（细胞间黏附分子-1、血管细胞黏附分子-1、E-选择素和P-选择素）的表达。然而，地塞米松预处理在控制肾脏炎症方面不如槲皮素有效。此外，改善的血液学参数如白细胞、红细胞和血小板计数表明，槲皮素在低压缺氧暴露下是一种功能良好的有效分子。组织病理学和透射电镜结果显示，大鼠肾脏肾小管排列发生结构变化，并且在低压缺氧应激下，这些变化通过槲皮素预防得到改善。因此，本研究表明，槲皮素可被视为一种潜在的植物化学黄酮类成分，用于预防低压缺氧下的急性肾脏炎症。
