Sigma-1 Receptor and Binding Immunoglobulin Protein Interact with Ulinastatin Contributing to a Protective Effect in Rat Cerebral Ischemia/Reperfusion

Autor: Ming-Jie Lin, Xiao-Shan Li, Zhu-Liang Xie, Huang-Sen Huang, Ling-Ao Dai, Yu-Fu Zeng, Zhuo-Li Zhu, Jia-Hao Yang, Wen-Jing Li, Xiao-Yin Chen, Xiong-Juan Li, Shu-Wen Chen
Rok vydání: 2021
Předmět:
Zdroj: World neurosurgery. 158
ISSN: 1878-8769
Popis: Objective The present study aimed to investigate the impact of ulinastatin (UTI) on sigma-1 receptor (σ1R) and bind to immunoglobulin protein (Bip) after cerebral ischemia/reperfusion (I/R) injury. Methods The middle cerebral artery occlusion (MCAO) model was used to induce cerebral I/R injury. A total of 80 male SD rats were randomly divided into six groups: Control, MCAO, MCAO+50,000 U/kg UTI (U5), MCAO+100,000 U/kg UTI (U10), MCAO+200,000 U/kg UTI (U20), MCAO+300,000 U/kg UTI (U30). At 24 and 48 h after MCAO, the infarct volume, neurological dysfunction, and grip strength test were measured, and the level of σ1R and Bip proteins was further detected using Western blot. The molecular docking assays were carried out to verify the interaction between σ1R, Bip, and UTI. The serum concentration of Bip as well as the binding assay between σ1R, Bip, and UTI were determined using enzyme-linked immunosorbent assay (ELISA). Results UTI increased the modified neurological severity score and upregulated the σ1R and Bip expression in the cerebral cortex under MCAO state. The grip strength of forelimbs increased significantly in the U20 and U30 groups compared to that of MCAO rats, while the Bip serum levels remained unchanged. The molecular docking assay indicated a putative binding between σ1R, Bip, and UTI. The binding assay also revealed that both σ1R and Bip could be combined with UTI. Conclusions UTI displays a neuroprotective effect via upregulation of σ1R and Bip during I/R injury, suggesting that UTI modulate σ1R and Bip and their interaction may provide a novel insight into the potential therapeutic mechanisms of stroke.
Databáze: OpenAIRE