Pinocembrin alleviates pyroptosis and apoptosis through ROS elimination in random skin flaps via activation of SIRT3

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Surgical Innovation

Background:

• Random skin flap grafting is crucial in reconstructive surgery, but distal flap necrosis remains a significant challenge, limiting its clinical application.
• Existing treatments for distal flap necrosis are insufficient, highlighting the need for novel therapeutic strategies.
• Pinocembrin (Pino), known for its antioxidant properties in other diseases, has not been investigated for its potential in improving flap survival.

Purpose of the Study:

• To investigate the efficacy of Pinocembrin (Pino) in enhancing random flap survival.
• To elucidate the underlying molecular mechanisms by which Pino promotes flap viability.
• To determine the role of SIRT3 and the AMPK/PGC-1α pathway in Pino's therapeutic effects on random flaps.

Main Methods:

• Macroscopic examination and Doppler assessment to evaluate flap viability.
• Immunohistochemistry and Western blot analyses to assess cellular mechanisms, including reactive oxygen species (ROS), pyroptosis, and apoptosis.
• Genetic manipulation using adeno-associated virus-silencing information regulator 2 homolog 3 (SIRT3) shRNA to investigate the role of SIRT3.
• Analysis of the AMP-activated protein kinase (AMPK) pathway activation.

Main Results:

• Pinocembrin (Pino) significantly improved random flap viability by inhibiting ROS, pyroptosis, and apoptosis.
• The protective effects of Pino were abolished by co-administration with SIRT3 shRNA, confirming SIRT3's critical role.
• Pino was found to upregulate SIRT3 expression via activation of the AMP-activated protein kinase (AMPK) pathway, specifically through the AMPK/PGC-1α signaling cascade.

Conclusions:

• Pinocembrin (Pino) demonstrates significant potential in improving random flap survival by mitigating oxidative stress and programmed cell death.
• The therapeutic benefits of Pino are critically dependent on the activation of SIRT3, which is triggered by the AMPK/PGC-1α pathway.
• This study establishes a novel mechanism for enhancing flap viability, offering a promising therapeutic avenue for reconstructive surgery.