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Chronic intermittent hypoxia exposure induces kidney injury in growing rats

  • Sleep Breathing Physiology and Disorders • Original Article
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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.

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Abbreviations

CIH:

chronic intermittent hypoxia

OSAHS:

obstructive sleep apnea hypopnea syndrome

HIF-1α:

hypoxia-inducible factor 1-alpha

SOD:

superoxide dismutase

Cu/ZnSOD:

copper-zinc superoxide dismutase

MnSOD:

manganese superoxide dismutase

PAS:

periodic acid–Schiff stain

HE:

hematoxylin and eosin stain

qRT-PCR:

real-time polymerase chain reaction

ROS:

reactive oxygen species

IRI:

ischemia reperfusion injury

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Acknowledgements

This work was supported by Zhejiang Provincial Natural Science Foundation Grant (LY17H010004), Scientific Research Foundation of Health Bureau of Zhejiang Province (2018ZD010), Wenzhou City Science and Technology Bureau Grant (Y20170133), National Science-technology Support Program (2015BAI12B09), and Project of Key Innovative Disciplines of Children Sleep Medicine of Zhejiang.

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Authors and Affiliations

  1. 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

    Neha-Devi Poonit, Yi-Chun Zhang, Chu-Yuan Ye, Hui-Lin Cai, Chen-Yi Yu & Xiao-Hong Cai

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

    Ting Li

  3. Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, China

    Xiao-Hong Cai

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  1. Neha-Devi Poonit
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Correspondence to Xiao-Hong Cai.

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All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Poonit, ND., Zhang, YC., Ye, CY. et al. Chronic intermittent hypoxia exposure induces kidney injury in growing rats. Sleep Breath 22, 453–461 (2018). https://doi.org/10.1007/s11325-017-1587-1

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