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氟伏沙明可通过增加白细胞介素-10和血管紧张素转换酶的表达以及维持水通道蛋白-2、水通道蛋白-4、紧密连接蛋白5和闭合蛋白-1的表达,逆转急性肾损伤时出现的滤过能力下降。

Fluvoxamine may reverse the decrease in filtering capacity that occurs in acute kidney injury by increasing IL-10 and ACE expressions and preserving AQ-2, AQ-4, CL-5, and ZO-1 expressions.

作者信息

Karakuyu Nasif Fatih, Camlica Tugce, Asci Halil, Milletsever Adem, Ulusoy Arzu, Gonuler Fatih Mehmet, Altuntas Atila

机构信息

Faculty of Pharmacy, Department of Pharmacology, Suleyman Demirel University, Isparta, Turkey.

Health Research and Application Center, Suleyman Demirel University Research and Application Hospital, Isparta, Turkey.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 29. doi: 10.1007/s00210-025-03844-2.

Abstract

The kidneys have a regulatory role in many diseases with their diuresis function and capacity to maintain electrolyte balance. In case of extensive damage, the kidney's filtration capacity is impaired and cannot fulfill its functions. Fluvoxamine (FLV), an antidepressant agent, has antioxidant and anti-inflammatory effects. This study aimed to investigate the protective effects of FLV against renal tissue damage in the lipopolysaccharide (LPS) induced systemic inflammation model. Thirty-two Wistar Albino rats were divided into four equal groups: control, LPS, LPS + FLV, and FLV alone. Six hours after LPS administration, rats were sacrificed and kidney tissues were removed. Histopathological examination of kidney tissues, immunohistochemical expression of the ACE-1, Cas-9, and interleukin-10 (IL-10), as well as spectrophotometric assessment of total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), urea, creatinine levels, and zonulin-1 (ZO-1), claudin-5 (CL-5), aquaporins 2 and 4 (AQ-2, AQ-4) were evaluated. TOS, OSI, urea, creatinine levels, and Cas-9 expressions were significantly increased, and TAS levels, ACE-1, IL-10, AQ-2, AQ-4, ZO-1, and CL-5 expressions significantly decreased in the LPS group compared with the control group. In addition, marked hyperemia, slight-to-moderate hemorrhages, and degeneration of the tubule epithelial cells were observed in kidney sections in the LPS group, in addition to the inflammatory cell infiltrations. FLV treatment significantly improved all these findings. FLV treatment ameliorates renal tissues against inflammatory scenes and protects renal function by enhancing IL-10 and ACE-1 expressions and preserving AQ-2, AQ-4, CL-5, and ZO-1 expressions.

摘要

肾脏凭借其利尿功能和维持电解质平衡的能力,在多种疾病中发挥调节作用。在发生广泛损伤时,肾脏的滤过能力受损,无法履行其功能。氟伏沙明(FLV)是一种抗抑郁药,具有抗氧化和抗炎作用。本研究旨在探讨FLV在脂多糖(LPS)诱导的全身炎症模型中对肾组织损伤的保护作用。将32只Wistar白化大鼠分为四组,每组数量相等:对照组、LPS组、LPS + FLV组和单独使用FLV组。给予LPS 6小时后,处死大鼠并取出肾脏组织。对肾脏组织进行组织病理学检查、评估血管紧张素转换酶-1(ACE-1)、Cas-9和白细胞介素-10(IL-10)的免疫组化表达,以及通过分光光度法评估总氧化剂状态(TOS)、总抗氧化剂状态(TAS)、氧化应激指数(OSI)、尿素、肌酐水平,以及闭合蛋白-1(ZO-1)、紧密连接蛋白-5(CL-5)、水通道蛋白2和4(AQ-2、AQ-4)。与对照组相比,LPS组的TOS、OSI、尿素、肌酐水平及Cas-9表达显著升高,而TAS水平、ACE-1、IL-10、AQ-2、AQ-4、ZO-1和CL-5表达显著降低。此外,在LPS组的肾脏切片中,除了炎性细胞浸润外,还观察到明显的充血、轻度至中度出血以及肾小管上皮细胞变性。FLV治疗显著改善了所有这些结果。FLV治疗可减轻肾组织的炎症反应,通过增强IL-10和ACE-1表达以及维持AQ-2、AQ-4、CL-5和ZO-1表达来保护肾功能。

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