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The Protective Effects of Ropivacaine Against High Glucose-induced Brain Microvascular Endothelial Injury by Reducing MMPs and Alleviating Oxidative Stress

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Abstract

Diabetes is undoubtedly affecting global health. Considerable attention has been directed to brain complications caused by diabetes, which are reported to be related to the injury on brain microvascular endothelial cells. Oxidative stress and degradation of vascular basement membrane contribute to the injury of vascular endothelia by diabetes. The present study aims to investigate the effects of ropivacaine on high glucose-induced brain microvascular endothelial injury, as well as the underlying mechanism.

Cell viability was determined by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The production of reactive oxygen species (ROS) was evaluated by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Quantitative real-time PCR (QRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to determine the expression levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), intercellular cell adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor (VEGF). The production of nitric oxide (NO) was detected by DAF-FM DA staining. The expression of inducible nitric oxide synthase (iNOS) was evaluated by qRT-PCR and Western blot analysis. Western blot was used to determine the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1).

The cell viability of bEnd.3 brain endothelial cells was inhibited by high glucose, which was rescued by ropivacaine. The elevated production of ROS and MDA by high glucose was reversed by ropivacaine. Ropivacaine suppressed the expression of up-regulated iNOS, NO, MMP-2, MMP-9, ICAM-1, and VEGF induced by high glucose incubation. The expression of Nrf-2 and HO-1 by high glucose incubation was significantly inhibited by ropivacaine treatment.

Ropivacaine might alleviate high glucose-induced brain microvascular endothelial injury by suppressing oxidative stress and down-regulating MMPs.

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Funding

This study is funded by “Natural Science Foundation of Shanghai (Grant/Award Number: 14ZR1407500)”.

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Authors and Affiliations

  1. Department of Anesthesiology, Fudan University Shanghai Cancer Center, No. 270 Dong’An Road, Shanghai, 200032, China

    Hu Lv, Qian Cheng, Ying Li, Yue Zhang, Jiawei Chen & Wei Chen

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Hu Lv, Qian Cheng, Ying Li, Yue Zhang, Jiawei Chen & Wei Chen

Authors
  1. Hu Lv
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  2. Qian Cheng
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  3. Ying Li
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  4. Yue Zhang
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  5. Jiawei Chen
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  6. Wei Chen
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Contributions

Hu Lv, Qian Cheng, Wei Chen: conceptualization and designed the experiments; Hu Lv, Qian Cheng, Ying Li, Yue Zhang, and Jiawei Chen: investigation; Wei Chen: supervision; Hu Lv, Qian Cheng, Wei Chen: analyzed the data; Wei Chen: writing-original draft; all authors reviewed and approved the manuscript.

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Correspondence to Wei Chen.

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Lv, H., Cheng, Q., Li, Y. et al. The Protective Effects of Ropivacaine Against High Glucose-induced Brain Microvascular Endothelial Injury by Reducing MMPs and Alleviating Oxidative Stress. Neurotox Res 39, 851–859 (2021). https://doi.org/10.1007/s12640-020-00324-8

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  • DOI: https://doi.org/10.1007/s12640-020-00324-8

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