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Research Paper|Volume 11, Issue 21|pp 9295—9309

Zinc-induced protective effect for testicular ischemia-reperfusion injury by promoting antioxidation via microRNA-101-3p/Nrf2 pathway

Zhiqiang Qin1, Kai Zhu2, Jianxin Xue2,3, Pu Cao3, Luwei Xu1, Zheng Xu1, Kai Liang1, Jiageng Zhu1, Ruipeng Jia1
  • 1Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
  • 2Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
  • 3Department of Urology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210003, China
* Equal contribution
# Co-corresponding author
Received: May 30, 2019Accepted: September 27, 2019Published: November 5, 2019

Copyright © 2019 Qin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The present study was performed to determine the protective effect of Zinc on the rat testicular ischemia-reperfusion (I/R) injury and its mechanism. In vivo, the pathological changes and the apoptosis index were significantly relieved in the rats with Low-dose Zinc pretreatment, compared to the I/R group. After Low-dose Zinc treatment, the levels of tissue Malondialdehyde (MDA) were significantly decreased, while tissue antioxidant indices were significantly increased. Meanwhile, the level of NF-κB was significantly lower compared to I/R group, while the levels of Nrf2-dependent antioxidant enzymes were significantly higher in Low-dose Zinc+I/R group. In vitro, Low-dose Zinc markedly increased Leydig cell (TM3) cell viability, and relieved testicular oxidative damage via down-regulating ROS. A total of 22 differently expressed microRNAs were screened out using microRNA microarray in rat testicular tissue caused by I/R injury, especially showing that miR-101-3p was selected as the target miRNA. Furthermore, the levels of Nrf2 and NF-κB were apparently increased/decreased in TM3 cells treated with Hypoxic/Reoxygenation (H/R) after miR-101-3p mimics/inhibitor. In addition, H/R-induced testicular oxidative damage was recovered in TM3 administrated with miR-101-3p inhibitor and si-Nrf2. Therefore, this study provided a novel insight for investigating protective effect of Zinc on testicular I/R injury by promoting antioxidation via miR-101-3p/Nrf2.