Biliverdin administration ameliorates cerebral ischemia reperfusion injury in rats and is associated with proinflammatory factor downregulation

Li,Jun‑Jie; Zou,Zhi‑Yao; Liu,Jia; Xiong,Liu‑Lin; Jiang,Hai‑Yan; Wang,Ting‑Hua; Shao,Jian‑Lin

doi:10.3892/etm.2017.4549

Biliverdin administration ameliorates cerebral ischemia reperfusion injury in rats and is associated with proinflammatory factor downregulation

Authors:
- Jun‑Jie Li
- Zhi‑Yao Zou
- Jia Liu
- Liu‑Lin Xiong
- Hai‑Yan Jiang
- Ting‑Hua Wang
- Jian‑Lin Shao
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Affiliations: Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Animal Center, Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan 650031, P.R. China, Department of Anesthesiology and Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: June 6, 2017 https://doi.org/10.3892/etm.2017.4549
Pages: 671-679
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Biliverdin (BV), one of the heme oxygenase-1 (HO‑1) catalytic products, has been demonstrated to have protective effects in liver ischemia reperfusion injury (IRI). The present study aimed to explore the effects of BV on cerebral IRI, and to investigate the potential mechanisms thereof. Adult male SD rats, weighing 200‑240 g, were randomly divided into sham (group S), cerebral ischemia reperfusion control (group C) and BV (group BV) groups. Rats in group C underwent transient middle cerebral artery occlusion (tMCAO) and received 2 ml normal saline; rats in group BV received BV (35 mg/kg) intraperitoneally 15 min prior to reperfusion and 4 h after reperfusion, then twice a day thereafter for 5 days. Group S served as the control. Neurological Severity Scores (NSS) were evaluated at days 1‑5 following reperfusion. Staining with 2, 3, 5‑triphenyltetrazolium chloride was performed to determine the cerebral infarction at 48 h post reperfusion. mRNA expression levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, IL‑1β, inducible nitric oxide synthase (iNOS) and HO‑1 in the ischemic cerebral cortex were detected via reverse transcription-quantitative polymerase chain reaction at 3, 6, 12 and 24 h after reperfusion. Western blotting was used to detect the protein expression levels at 3 h after reperfusion. Compared with group S, the NSS, cerebral infarct volume, and the mRNA and protein expression levels of TNF‑α, IL‑6, IL‑1β, iNOS and HO‑1 of Group C were significantly increased (P<0.05). However, BV administration significantly improved and reduced these expression levels (P<0.01). The present study indicates that BV is able to ameliorate cerebral IRI in rats and that the mechanism may be associated with the downregulation of proinflammatory factors.

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