Department of Pediatrics, Guangxi Medical University, Nanning, China.
Department of Pediatrics, The First Affiliated Hospital, Guangxi Medical University, Nanning, China.
Ren Fail. 2022 Dec;44(1):2056-2065. doi: 10.1080/0886022X.2022.2148539.
In recent years, peroxisome proliferator-activated receptor γ (PPARγ) has been found to be closely associated with hypoxia renal disease. The aim of this study was to investigate the relationship between rosiglitazone and mitochondrial apoptosis in renal tissue and its associated mechanisms.
Twenty-four male Sprague-Dawley rats were randomly divided into three groups ( = 8 in each): normal control group, hypoxia injury group (equal volume of 0.9% saline), and PPARγ agonist group (Rosiglitazone, 10 mg/kg · d, intraperitoneally). The hypoxia injury group and PPARγ agonist group were placed in a hypoxia chamber and the simulated altitude was set at 7,000 m for 7 days. Blood and kidney samples were collected after 7 days. The quantitative real-time polymerase chain reaction and Western blot methods were used to determine the expression of PPARγ, nuclear factor kappa-B (NF-κB), B-cell lymphoma-2 (Bcl-2), and Bax.
The results showed that compared with the normal control group, the renal tissue of rats after hypoxia was severely damaged, as shown by massive renal tubular epithelial cell degeneration and detachment, and renal tubular dilation. The NF-κB protein expression significantly increased, the Bcl-2 protein and mRNA expression significantly decreased, and Bax protein and mRNA expression significantly increased ( < .05 for all). Renal injury was much less severe in the PPARγ agonist group compared to the hypoxia injury group.
Rosiglitazone can alleviate hypoxia renal injury, with the possible mechanism involving attenuation of apoptosis by inhibiting the activation of the NF-κB signaling pathway in a PPARγ-dependent manner and increasing Bcl-2 and decreasing Bax expression.
近年来，过氧化物酶体增殖物激活受体γ（PPARγ）被发现与低氧性肾病密切相关。本研究旨在探讨罗格列酮与肾组织线粒体凋亡的关系及其相关机制。
将 24 只雄性 Sprague-Dawley 大鼠随机分为三组（每组 8 只）：正常对照组、缺氧损伤组（等体积 0.9%生理盐水）和 PPARγ 激动剂组（罗格列酮，10mg/kg·d，腹腔注射）。缺氧损伤组和 PPARγ 激动剂组置于缺氧箱中，模拟海拔 7000m，7d。7d 后采集血样和肾样。采用实时定量聚合酶链反应和 Western blot 方法测定 PPARγ、核因子 kappa-B（NF-κB）、B 细胞淋巴瘤-2（Bcl-2）和 Bax 的表达。
结果显示，与正常对照组相比，缺氧后大鼠的肾组织损伤严重，大量肾小管上皮细胞变性、脱落，肾小管扩张。NF-κB 蛋白表达明显增加，Bcl-2 蛋白和 mRNA 表达明显减少，Bax 蛋白和 mRNA 表达明显增加（均<0.05）。PPARγ 激动剂组的肾损伤明显轻于缺氧损伤组。
罗格列酮可减轻缺氧性肾损伤，其机制可能是通过抑制 NF-κB 信号通路的激活，增加 Bcl-2 表达，减少 Bax 表达，从而抑制细胞凋亡。
