Ropivacaine inhibits wound healing by suppressing the proliferation and migration of keratinocytes via the PI3K/AKT/mTOR Pathway.

Abstract

BACKGROUND:

After surgery, millions of people suffer from delayed healing or wound dehiscence with subsequent severe complications, even death. Previous studies have reported that ropivacaine exhibits anti-proliferative and anti-migratory activities on numerous cells. Whether ropivacaine is able to influence the proliferation and migration of keratinocytes is still unclear. This study aimed to investigate the effect of ropivacaine on keratinocytes and its underlying molecular mechanism.

METHODS:

Adult male Sprague-Dawley rats were allocated to establish wound healing models with or without 0.75% ropivacaine treatment and assessed the epidermal thickness by HE staining. HaCaT cells were cultured to evaluate the effect of ropivacaine on wound healing. The cell proliferation, apoptosis status and migration were detected in vitro. Moreover, western blotting was used to examine expression to with PI3K/AKT/mTOR signaling pathways for molecular studies and the changes in inflammatory factors (IL-6, IL-10, TNF-α) were detected by ELISA.

RESULTS:

In the present study, we found that ropivacaine delayed wound closure in vivo. In vitro experiments, it was demonstrated that ropivacaine significantly inhibited the proliferation and migration of HaCaT cells via the suppression of PI3K/AKT/mTOR signaling pathway. Activation of PI3K/AKT/mTOR signaling pathway reversed the effects of ropivacaine on the proliferation and migration of HaCaT cells. Furthermore, ropivacaine contributed to the release of pro-inflammatory cytokines (IL-6 and TNF-α) and inhibited the secretion of anti-inflammatory cytokines of keratinocytes (IL-10).

CONCLUSIONS:

Our research demonstrated that ropivacaine treatment showed a more decreased wound closure rate. Mechanistically, we found that ropivacaine suppressed the proliferation and migration of keratinocytes and altered the expression of cytokines by inhibiting PI3K/AKT/mTOR pathway.

• Authors: Xiaoyang Wu, Quanyu Sun, Simeng He, Ya Wu, Shihan Du, Lirong Gong, Jianbo Yu, Haifeng Guo
• Journal: BMC anesthesiology (BMC Anesthesiol) Vol. 22 Issue 1 Pg. 106 (04 15 2022) ISSN: 1471-2253 [Electronic] England
• PMID: 35428182 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Cytokines
• Interleukin-6
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Ropivacaine
• MTOR protein, human
• mTOR protein, rat
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Animals
• Cell Proliferation
• Cytokines (metabolism)
• Humans
• Interleukin-10
• Interleukin-6 (metabolism)
• Keratinocytes (metabolism)
• Male
• Phosphatidylinositol 3-Kinases (metabolism, pharmacology)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Sprague-Dawley
• Ropivacaine (pharmacology)
• TOR Serine-Threonine Kinases (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Wound Healing