• World Neurosurg · Feb 2022

    Sigma-1 receptor and binding immunoglobulin protein interacts with ulinastatin contributing to a protective effect on rat cerebral ischemia-reperfusion.

    • Ling-Ao Dai, Xiao-Yin Chen, Wen-Jing Li, Jia-Hao Yang, Ming-Jie Lin, Xiao-Shan Li, Yu-Fu Zeng, Shu-Wen Chen, Zhu-Liang Xie, Zhuo-Li Zhu, Xiong-Juan Li, and Huan-Sen Huang.
    • Department of Anesthesiology, Second Clinical College of Guangzhou Medical University, Guangzhou, China.
    • World Neurosurg. 2022 Feb 1; 158: e488e494e488-e494.

    ObjectiveTo investigate impact of ulinastatin (UTI) on sigma-1 receptor (σ1R) and binding immunoglobulin protein (BiP) after cerebral ischemia/reperfusion injury.MethodsThe middle cerebral artery occlusion (MCAO) model was used to induce cerebral ischemia/reperfusion injury. Eighty male Sprague Dawley rats were randomly divided into 6 groups: control, MCAO, MCAO+50,000 U/kg UTI, MCAO+100,000 U/kg UTI, MCAO+200,000 U/kg UTI, MCAO+300,000 U/kg UTI. At 24 and 48 hours after MCAO, infarct volume, neurological dysfunction, and grip strength test were measured, and level of σ1R and BiP proteins was further detected using Western blot. Molecular docking assays were carried out to verify interaction between σ1R, BiP, and UTI. The serum concentration of BiP and the binding assay between σ1R, BiP, and UTI were determined using enzyme-linked immunosorbent assay.ResultsUTI increased the modified neurological severity score and upregulated σ1R and BiP expression in the cerebral cortex after MCAO. The grip strength of forelimbs increased significantly in the MCAO+200,000 U/kg UTI and MCAO+300,000 U/kg UTI groups compared with the MCAO group, while BiP serum levels remained unchanged. The molecular docking assay indicated putative binding between σ1R, BiP, and UTI. The binding assay also revealed that both σ1R and BiP could be combined with UTI.ConclusionsUTI displays a neuroprotective effect via upregulation of σ1R and BiP during ischemia/reperfusion injury, suggesting that UTI modulates σ1R and BiP and their interaction may provide a novel insight into potential therapeutic mechanisms for stroke.Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

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