The role and mechanism of quercetin in promoting diabetic wound healing by regulating the PI3K/Akt/GSK-3β signaling pathway and NLRP3 activation
10.13431/j.cnki.immunol.j.20240105
- VernacularTitle:槲皮素在糖尿病创面修复中的作用及机制
- Author:
Ding ZHU
1
;
Yijing LIN
;
Xinying LI
;
Chunhua MA
;
Yuangang LU
Author Information
1. 400042 重庆,陆军军医大学大坪医院整形美容科
- Publication Type:Journal Article
- Keywords:
Diabetic Wounds;
Quercetin;
PI3K/Akt/GSK-3β;
NLRP3
- From:
Immunological Journal
2024;40(10):752-760
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the promoting effect of quercetin(QR)on diabetic wound repair and its possible mechanism.Methods HUVEC cell injury model was induced by 33.36 mmol/L high glucose.The cells were divided into normal control group(NG group),mannitol group(MA group),high glucose group(HG group),low dose quercetin+high glucose group(QR 5 μmol/L+HG group),high dose quercetin+high glucose group(QR 20 μmol/L+HG group).Treatment for 24 hours;CCK-8 and Edu were used to measure cell viability.Cell scratch test and Transwell migration assay were used to detect cell migration ability.Matrigel tube formation assay was used to measure the angiogenesis ability.The levels of IL-1β,IL-18 and TNF-α were detected by ELISA.Network pharmacology was used to screen the potential targets of QR on diabetic wounds.Western blot was used to detect the expression of NLRP3 inflammasome,PI3K/Akt/GSK-3β pathway and its phosphorylation.The diabetic wound model of C57 mice was established and divided into STZ group and QR+STZ group.The wound healing rate within 14 days was calculated and analyzed,and the wound tissue was stained with HE and Masson on the 14th day.Results CCK-8 and Edu results showed that a high dose of QR could improve the viability of huvecs induced by high glucose.Scratch test and Transwell migration test showed that high dose of QR could enhance the migration ability of HUVEC cells induced by high glucose.Matrigel tube formation assay showed that high dose of QR could enhance the angiogenesis ability of HUVEC cells induced by high glucose.ELISA results showed that high dose of QR could inhibit the secretion of IL-1β,IL-18 and TNF-α induced by high glucose.Network pharmacology screening results showed that PI3K/Akt/GSK-3β pathway was significantly enriched.Western blot showed that 20 μmol/L QR could increase the phosphorylation level of PI3K/Akt/GSK-3β pathway and inhibit the expression of NLRP3 inflammasome,which could be reversed by the addition of PI3K phosphorylation inhibitor LY294002.Animal experiments have shown that QR can promote diabetic wound healing by enhancing granulation tissue growth,epithelial regeneration,and collagen deposition.Conclusion QR can improve HUVEC injury induced by high glucose and promote wound healing in diabetic mice,and its mechanism may be related to inhibiting NLRP3 expression through PI3K/Akt/GSK-3β pathway.
