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Propofol Downregulates lncRNA MALAT1 to Alleviate Cerebral Ischemia–Reperfusion Injury

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Abstract

Propofol (PPF) is reported to play a protective role in ischemia/reperfusion (I/R) injury, including cerebral ischemia–reperfusion injury (CIRI). This study aims to investigate the mechanism by which PPF ameliorates CIRI. Kunming mice were used to establish the middle cerebral artery occlusion (MCAO)/reperfusion mouse model in vivo. PPF pre-treatment was performed before CIRI. Lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) levels were detected to evaluate the tissue injury. PC12 cells were exposed to hypoxia/reoxygenation (H/R) to construct the in vitro CIRI model, and PC12 cells were pre-treated with PPF before H/R. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expression of lncRNA MALAT1 and miR-182-5p. Flow cytometry was used to detect the apoptosis of PC12 cells. Bioinformatics analysis, qRT-PCR, dual-luciferase reporter gene experiments, and RNA immunoprecipitation (RIP) experiments were performed to predict and validate the targeting relationship between MALAT1 and miR-182-5p. Western blot was used to detect Toll-like receptor 4 (TLR4) expression at protein level. PPF pre-treatment remarkably inhibited LDH and CPK levels in the serum of the mice with CIRI, and reduced the apoptosis of PC12 cells exposed to H/R. Besides, PPF pre-treatment markedly suppressed MALAT1 expression in both in vivo and in vitro models and upregulated miR-182-5p expression. MiR-182-5p was validated to be a downstream target gene of MALAT1, and MALAT1 could increase the expression of TLR4 by suppressing miR-182-5p. The effects of PPF on the injury of the mice brain and PC12 cells were partly counteracted by the restoration of MALAT1. PPF protects the brain against I/R-induced injury by regulating MALAT1/miR-182-5p/TLR4 axis.

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Availability of Data and Materials

The data used to support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

We thank Hubei Yican Health Industry Co., Ltd (Wuhan, Hubei, China) for its linguistic assistance during the preparation of this manuscript.

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Author notes

  1. Hu Yubo and Ye Cong contribute equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Erdao District, 126 Sendai Street, Changchun, Jilin Province, 130033, China

    Yubo Hu, Shuang Cheng & Junyang Chen

  2. Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, China

    Cong Ye

  3. Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Erdao District, 126 Sendai Street, Changchun, Jilin Province, 130033, China

    Junyang Chen

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  1. Yubo Hu
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Contributions

Conceived and designed the experiments: Yubo Hu, Junyang Chen; performed the experiments: Yubo Hu, Cong Ye, Shuang Cheng, Junyang Chen; analyzed the data: Yubo Hu, Cong Ye, Shuang Cheng; wrote the paper: Yubo Hu, Shuang Cheng, Junyang Chen.

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Correspondence to Junyang Chen.

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Our study was approved by the Ethics Review Board of China-Japan Union Hospital of Jilin University (Approval number: 20190107C009).

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Hu, Y., Ye, C., Cheng, S. et al. Propofol Downregulates lncRNA MALAT1 to Alleviate Cerebral Ischemia–Reperfusion Injury. Inflammation 44, 2580–2591 (2021). https://doi.org/10.1007/s10753-021-01525-9

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  • DOI: https://doi.org/10.1007/s10753-021-01525-9

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