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. 2021 Jul;48(1):135.
doi: 10.3892/ijmm.2021.4968. Epub 2021 May 26.

Propofol maintains Th17/Treg cell balance and reduces inflammation in rats with traumatic brain injury via the miR‑145‑3p/NFATc2/NF‑κB axis

Can Cui #  1 , Dengwen Zhang #  1 , Ke Sun  1 , Haifeng Li  1 , Liqian Xu  1 , Gen Lin  1 , Yuanbo Guo  1 , Jiaqi Hu  1 , Jieyuan Chen  1 , Lidan Nong  1 , Yujin Cai  1 , Dongnan Yu  1 , Wei Yang  1 , Peng Wang  2 , Yi Sun  1
Affiliations

Propofol maintains Th17/Treg cell balance and reduces inflammation in rats with traumatic brain injury via the miR‑145‑3p/NFATc2/NF‑κB axis

Can Cui et al. Int J Mol Med. 2021 Jul.

Abstract

Propofol is a commonly used intravenous anesthetic. The aim of the study was to examine the mechanism of propofol in traumatic brain injury (TBI) by regulating interleukin (IL)‑17 activity and maintaining the Th17/Treg balance. A rat model with moderate TBI was established using the weight‑drop method. Rats with TBI were regularly injected with propofol and their brain injuries were monitored. The peripheral blood of rats was collected to measure the Th17/Treg ratio. MicroRNA (miR)‑145‑3p expression was detected in the brain tissues of rats and antagomiR‑145‑3p was injected into the lateral ventricles of their brains to verify the effect of miR‑145‑3p on brain injury. The downstream target of miR‑145‑3p was predicted. The targeting relationship between miR‑145‑3p and nuclear factor of activated T cells c2 (NFATc2) was confirmed. NFATC2 expression and phosphorylation of NF‑κB pathway‑related proteins were measured. Propofol alleviated brain injury in rats with TBI and maintained the Th17/Treg balance. Propofol upregulated miR‑145‑3p expression in rat brains, while the inhibition of miR‑145‑3p reversed the effect of propofol on brain injury. A binding relationship was observed between miR‑145‑3p and NFATc2. Furthermore, propofol decreased the phosphorylation of p65 and IκBα, and inhibited activation of the NF‑κB pathway in the brains of rats with TBI. In conclusion, propofol maintained Th17/Treg balance and reduced inflammation in the rats with TBI via the miR‑145‑3p/NFATc2/NF‑κB axis.

Keywords: NF‑κB; Th17/Treg; inflammation; microRNA‑145‑3p; nuclear factor of activated T cells c2; propofol; traumatic brain injury.

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Conflict of interest statement

All authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Propofol reduced brain injury in rats with TBI, inhibited IL-17 expression, and maintained Th17/Treg balance. (A) Neurological score, n=18; (B) brain water content, n=6; (C) brain tissue sections of rats with TBI were stained with H&E and TUNEL, and the apoptotic rate was expressed using the TUNEL-positive cell rate, n=6; (D) IL-17 expression in the rats' peripheral blood was detected using ELISA, n=18; (E) the ratio of Th17/Treg cells in the rats' peripheral blood was detected by flow cytometry, n=18; (F) the cells that were positive for inflammatory factors in the rats' brains were detected using immunohistochemistry, n=6. Each experiment was repeated three times. Data were analyzed using one-way ANOVA, followed by Tukey's multiple comparisons test. ***Compared with the sham group, P<0.001; ###Compared with the TBI group, P<0.001.
Figure 2
Figure 2
Propofol upregulated miR-145-3p expression in the brain of rats with TBI. (A-B) Expressions of miRs in the brain tissues of rats were detected using RT-qPCR. (A) Five miRs differentially expressed in the literature as validation; (B) expression of miR-145-3p under different treatments, n=6. Each experiment was repeated three times. Data were analyzed using one-way ANOVA, followed by Tukey's multiple comparisons test. ***Compared with the sham group, P<0.001; ###Compared with the TBI group, P<0.001.
Figure 3
Figure 3
Inhibition of miR-145-3p reversed the effect of propofol on brain injury. (A) Expression of miR-145-3p in brain tissues of rats after injection of antagomiR into lateral ventricle was detected using RT-qPCR; (B) neurological score, n=18; (C) brain water content, n=6; (D) brain tissue sections of rats with TBI were stained with H&E and TUNEL, and the apoptotic rate was expressed using the TUNEL-positive cell rate, n=6; (E) IL-17 expression in the rats' peripheral blood was detected using ELISA, n=18; (F) the ratio of Th17/Treg cells in the rats' peripheral blood was detected by flow cytometry, n=18; (G) the cells that were positive for inflammatory factors in the rats' brains were detected using immunohistochemistry, n=6. Each experiment was repeated three times. Data were analyzed using one-way ANOVA, followed by Tukey's multiple comparisons test. *P<0.05, **P<0.01, ***P<0.001, compared with the TBI group; ##P<0.01, ###P<0.001, compared with the TBI+P group.
Figure 4
Figure 4
miR-145-3p inhibited the expression of NFATc2. (A) Analysis and prediction of binding site between miR-145-3p and NFATc2 online (http://www.targetscan.org/); (B) the targeting relationship between miR-145-3p and NFATc2 was confirmed using the dual-luciferase reporter gene assay; (C and D) NFATc2 expression in brain tissues of rats in each treatment group was detected using RT-qPCR and western blotting. Each experiment was repeated three times. Data were analyzed using one-way ANOVA, followed by Tukey's multiple comparisons test. **P<0.01, ***P<0.001, compared with each NC group.
Figure 5
Figure 5
Propofol inhibited phosphorylation of NF-κB pathway-related proteins. Phosphorylation and protein level of NF-κB pathway-related proteins in brain tissues of rats with TBI under different treatments were detected using western blotting, n=6. Data were analyzed using one-way ANOVA, followed by Tukey's multiple comparisons test. **P<0.01.
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References

    1. Gardner AJ, Zafonte R. Neuroepidemiology of traumatic brain injury. Handb Clin Neurol. 2016;138:207–223. doi: 10.1016/B978-0-12-802973-2.00012-4. - DOI - PubMed
    1. Georgiou AP, Manara AR. Role of therapeutic hypothermia in improving outcome after traumatic brain injury: A systematic review. Br J Anaesth. 2013;110:357–367. doi: 10.1093/bja/aes500. - DOI - PubMed
    1. Ziebell JM, Morganti-Kossmann MC. Involvement of pro- and anti-inflammatory cytokines and chemokines in the pathophysiology of traumatic brain injury. Neurotherapeutics. 2010;7:22–30. doi: 10.1016/j.nurt.2009.10.016. - DOI - PMC - PubMed
    1. Boer C, Franschman G, Loer SA. Prehospital management of severe traumatic brain injury: Concepts and ongoing controversies. Curr Opin Anaesthesiol. 2012;25:556–562. doi: 10.1097/ACO.0b013e328357225c. - DOI - PubMed
    1. Si L, Wang H, Wang L. Suppression of miR-193a alleviates neuroinflammation and improves neurological function recovery after traumatic brain injury (TBI) in mice. Biochem Biophys Res Commun. 2020;523:527–534. doi: 10.1016/j.bbrc.2019.11.095. - DOI - PubMed

Grants and funding

This study was supported by the Science and Technology Planning Project of Guangdong Province, China (2012B031800161), the Medical Scientific Research Foundation of Guangdong Province, China (A2016573), the Natural Science Foundation of Guangdong Province, China (2018A0303130236), the Natural Science Foundation of Guangdong Province, China (2018A0303130297); the Science and Technology Program of Guangzhou, China (201904010080), the Project of Administration of Traditional Chinese Medicine of Guangdong Province, China (20191006), the Foundation for Basic and Applied Basic Research of Guangdong Province, China (2019A1515110063), and the Medical Scientific Research Foundation of Guangdong Province, China (A2020038).