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慢性间歇性低氧暴露可诱导生长大鼠肾脏损伤。

Chronic intermittent hypoxia exposure induces kidney injury in growing rats.

机构信息

Department of Pediatrics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Western Road, Wenzhou, Zhejiang, 325027, People's Republic of China.

The Children's Hospital, Zhejiang University School Of Medicine, Hangzhou, 310000, China.

出版信息

Sleep Breath. 2018 May;22(2):453-461. doi: 10.1007/s11325-017-1587-1. Epub 2017 Nov 9.

DOI:10.1007/s11325-017-1587-1
PMID:29124628
Abstract

OBJECTIVE

The objectives of this paper are to examine the effect of chronic intermittent hypoxia (CIH) on the morphological changes in the kidney of growing rats and to explore the mechanisms underlying the CIH-induced renal damage.

METHODS

Forty Sprague-Dawley rats were randomly divided into two groups: 2 and 4 weeks CIH groups (2IH, 4IH), and in the control group 2 and 4 weeks air-stimulated groups (2C, 4C), with 10 rats in each group. Pathological changes of renal tissue were observed by HE staining, PAS staining, and Masson staining. Real-time PCR method was used to detect the mRNA expression of HIF-1α, CuZnSOD/ZnSOD, and MnSOD in renal tissue.

RESULTS

(1) Intermittent hypoxia (IH) caused morphological damage in the kidney. Hypertrophy of epithelial cells in the kidney tubules and dilation in the glomeruli were observed under light microscope in HE and PAS stain, especially in 4IH group. Masson staining showed no significant fibrotic response in the IH groups. (2) Compared with the corresponding control groups, the levels of serum SOD were significantly lower in CIH groups, and especially in 4IH group. The mRNA expression of Cu/ZnSOD and MnSOD in CIH groups decreased significantly as compared to control groups. The mRNA levels of HIF-1α in the kidney were significantly higher in CIH groups than those in the corresponding control groups.

CONCLUSION

Oxidative stress played a critical role in renal damage by up-regulating HIF-1α transcription and down-regulating Cu/ZnSOD and MnSOD transcription after chronic intermittent hypoxia exposure in growing rats.

摘要

目的

本文旨在研究慢性间歇性低氧(CIH)对生长大鼠肾脏形态变化的影响,并探讨 CIH 诱导肾损伤的机制。

方法

40 只 Sprague-Dawley 大鼠随机分为两组:2 周和 4 周 CIH 组(2IH、4IH)和对照组的 2 周和 4 周空气刺激组(2C、4C),每组 10 只大鼠。通过 HE 染色、PAS 染色和 Masson 染色观察肾组织的病理变化。实时 PCR 法检测肾组织中 HIF-1α、CuZnSOD/ZnSOD 和 MnSOD 的 mRNA 表达。

结果

(1)间歇性低氧(IH)导致肾脏形态损伤。在 HE 和 PAS 染色下,光镜下观察到肾小管上皮细胞肥大和肾小球扩张,尤其是在 4IH 组。IH 组 Masson 染色未见明显纤维化反应。(2)与相应对照组相比,CIH 组血清 SOD 水平明显降低,尤其是 4IH 组。与对照组相比,CIH 组 Cu/ZnSOD 和 MnSOD 的 mRNA 表达明显降低。CIH 组肾组织中 HIF-1α 的 mRNA 水平明显高于相应对照组。

结论

在生长大鼠慢性间歇性低氧暴露后,氧化应激通过上调 HIF-1α 转录和下调 Cu/ZnSOD 和 MnSOD 转录,在肾脏损伤中起关键作用。

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