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木樨草素可减轻载脂蛋白 E 缺陷小鼠血管紧张素 II 诱导的肾损伤。

Luteolin attenuates angiotensin II‑induced renal damage in apolipoprotein E‑deficient mice.

机构信息

Department of Endocrinology, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian, Liaodong 116011, P.R. China.

Department of Internal Medicine, The Affiliated Zhong Shan Hospital of Dalian University, Dalian, Liaodong 116011, P.R. China.

出版信息

Mol Med Rep. 2021 Feb;23(2). doi: 10.3892/mmr.2020.11796. Epub 2020 Dec 23.

Abstract

Renal damage is a common and severe condition encountered in the clinic. Luteolin (Lut) exhibits anti‑inflammatory, anti‑fibrotic and anti‑apoptotic effects. Thus, the present study aimed to investigate the pharmacological effects of Lut on angiotensin II (AngII)‑induced renal damage in apolipoprotein E‑deficient (ApoE) mice. Male ApoE mice (age, 8 weeks) were randomly divided into the following three groups: i) Control group (n=6); ii) AngII group (n=6); and iii) AngII + Lut group (n=6). Lut was administered by gavage (100 mg/kg/d). ApoE mice were implanted with Alzet osmotic minipumps, filled with either saline vehicle or AngII solution for a maximum period of 4 weeks. After 4 weeks, metabolic characteristics were measured and the histopathological alterations in the kidney tissue were observed. The metabolic characteristics of blood creatinine (CRE) levels were lower in the AngII + Lut group compared with in the AngII group. The expression levels of collagen I and III were lower in the kidney tissues of the AngII + Lut group compared with the corresponding tissues of the AngII group. The gene expression levels of IL‑1β, IL‑6, TNF‑α and IL‑10 were also suppressed in the kidney tissues of the AngII + Lut group compared with those in the corresponding tissues of the AngII group. Furthermore, the AngII + Lut group exhibited markedly increased LC3 protein expression and notably decreased p62 protein expression in the kidney tissues compared with the expression levels in the AngII group. The data demonstrated that Lut attenuated AngII‑induced collagen deposition and inflammation, while inducing autophagy. Collectively, the results suggested that Lut treatment exhibited a exerted effect on AngII‑induced renal injury in ApoE mice.

摘要

肾脏损伤是临床中常见且严重的病症。木犀草素(Lut)具有抗炎、抗纤维化和抗细胞凋亡作用。因此,本研究旨在探讨 Lut 对载脂蛋白 E 缺陷(ApoE)小鼠血管紧张素 II(AngII)诱导的肾脏损伤的药理作用。雄性 ApoE 小鼠(8 周龄)随机分为以下三组:i)对照组(n=6);ii)AngII 组(n=6);和 iii)AngII+Lut 组(n=6)。通过灌胃给予 Lut(100mg/kg/d)。ApoE 小鼠植入 Alzet 渗透微型泵,泵内填充生理盐水或 AngII 溶液,持续 4 周。4 周后,测量代谢特征并观察肾脏组织的组织病理学改变。与 AngII 组相比,AngII+Lut 组的血液肌酐(CRE)水平代谢特征较低。AngII+Lut 组肾脏组织中胶原 I 和 III 的表达水平低于 AngII 组。AngII+Lut 组肾脏组织中白细胞介素 1β(IL-1β)、白细胞介素 6(IL-6)、肿瘤坏死因子-α(TNF-α)和白细胞介素 10(IL-10)的基因表达水平也低于 AngII 组。此外,与 AngII 组相比,AngII+Lut 组肾脏组织中 LC3 蛋白表达显著增加,p62 蛋白表达显著降低。这些数据表明,与 AngII 组相比,Lut 减轻了 AngII 诱导的胶原蛋白沉积和炎症,同时诱导了自噬。综上所述,结果表明 Lut 对 ApoE 小鼠 AngII 诱导的肾脏损伤具有治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f53d/7789115/4c35664f7703/mmr-23-02-11796-g00.jpg

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