Department of Pharmacology, Faculty of Pharmacy, University of Misan, Iraq.
Department of Pharmacology, Faculty of Medicine, Al-Nahrain University, Iraq.
Arch Razi Inst. 2021 Dec 30;76(6):1755-1764. doi: 10.22092/ari.2021.356202.1803. eCollection 2021 Dec.
One of the main causes of acute kidney injury is ischemic reperfusion injury (IRI). Inflammatory response, apoptotic damages, and oxidative stress-related injuries are all involved in the pathogenesis of IRI. Toll-like receptors (TLR) are strongly associated with IRIs, especially TLR4, which is markedly induced in response to IRI. Accordingly, the current study aimed to investigate the potential renoprotective effect of ultrapure lipopolysaccharide from (ULPS-RS) at two doses in an animal model of bilateral IRI. A total of 30 adult male rats were divided randomly into five equal groups of control (laparotomy plus bilateral renal IRI), vehicle (same as the control group, but pretreated with the vehicle), sham (laparotomy only), ULPS-RS (same as the control group, but pretreated with 0.1 mg/kg of ULPS-RS), and ULPS-RSH (same as the control group, but pretreated with 0.2 mg/kg of ULPS-RS). Subsequent to 30 min of ischemia and 2 h of reperfusion, serum samples were collected for measuring urea, creatinine, and neutrophil gelatinase-associated lipocalin. Afterward, tissue samples were obtained from all animals to measure inflammatory mediators (interleukin 6, interleukin 1β, and tumor necrosis factor α), oxidative stress marker (8-isoprostane), apoptosis mediators (B cell lymphoma 2 [Bcl2]), and Bcl2-associated X protein (Bax). In the control group, all of the measured parameters were significantly elevated in response to IRI, except for Bcl2, which decreased significantly. On the other hand, exactly opposite effects were observed in the ULPS-RS treated groups indicating the nephroprotective effect of this compound against IRI at both tested doses. The findings reveal for the first time that ULPS-RS has the therapeutic potential of attenuating the renal dysfunction induced by IRI.
急性肾损伤的主要原因之一是缺血再灌注损伤 (IRI)。炎症反应、细胞凋亡损伤和氧化应激相关损伤都参与了 IRI 的发病机制。Toll 样受体 (TLR) 与 IRI 密切相关，尤其是 TLR4，它在 IRI 时明显被诱导。因此，本研究旨在探讨两种剂量的 （ULPS-RS） 超纯脂多糖在双侧 IRI 动物模型中的潜在肾脏保护作用。总共 30 只成年雄性大鼠随机分为五组：对照组（剖腹术加双侧肾 IRI）、载体组（与对照组相同，但用载体预处理）、假手术组（仅剖腹术）、ULPS-RS 组（与对照组相同，但用 0.1mg/kg ULPS-RS 预处理）和 ULPS-RSH 组（与对照组相同，但用 0.2mg/kg ULPS-RS 预处理）。缺血 30 分钟和再灌注 2 小时后，收集血清样本测量尿素、肌酐和中性粒细胞明胶酶相关脂质运载蛋白。随后，从所有动物获得组织样本以测量炎症介质（白细胞介素 6、白细胞介素 1β 和肿瘤坏死因子-α）、氧化应激标志物（8-异前列腺素）、凋亡介质（B 细胞淋巴瘤 2 [Bcl2]）和 Bcl2 相关 X 蛋白（Bax）。在对照组中，除 Bcl2 明显降低外，所有测量参数在 IRI 时均显著升高。另一方面，在 ULPS-RS 处理组中观察到完全相反的效果，表明该化合物在两种测试剂量下均具有对抗 IRI 的肾脏保护作用。这些发现首次表明 ULPS-RS 具有减轻 IRI 引起的肾功能障碍的治疗潜力。
