上睑下垂
自噬
TFEB
氧化应激
细胞生物学
化学
安普克
细胞凋亡
活性氧
再灌注损伤
钙调神经磷酸酶
程序性细胞死亡
药理学
缺血
生物
医学
蛋白激酶A
生物化学
内科学
移植
激酶
作者
Ningning Yang,Gaoxiang Yu,Yingying Le,Jiayi Zhao,Zhuliu Chen,Liang Chen,Ya Fu,Pingfei Fang,Weiyang Gao,Yuepiao Cai,Zhijie Li,Jian Xiao,Kailiang Zhou,Kailiang Zhou
摘要
Background and Purpose Ischaemia–reperfusion (I/R) injury is a major contributor to skin flap necrosis, which presents a challenge in achieving satisfactory therapeutic outcomes. Previous studies showed that cathelicidin‐BF (BF‐30) protects tissues from I/R injury. In this investigation, BF‐30 was synthesized and its role and mechanism in promoting survival of I/R‐injured skin flaps explored. Experimental Approach Survival rate analysis and laser Doppler blood flow analysis were used to evaluate I/R‐injured flap viability. Western blotting, immunofluorescence, TdT‐mediated dUTP nick end labelling (TUNEL) and dihydroethidium were utilized to examine the levels of apoptosis, pyroptosis, oxidative stress, transcription factor EB (TFEB)‐mediated autophagy and molecules related to the adenosine 5′‐monophosphate‐activated protein kinase (AMPK)–transient receptor potential mucolipin 1 (TRPML1)–calcineurin signalling pathway. Key Results The outcomes revealed that BF‐30 enhanced I/R‐injured island skin flap viability. Autophagy, oxidative stress, pyroptosis and apoptosis were related to the BF‐30 capability to enhance I/R‐injured flap survival. Improved autophagy flux and tolerance to oxidative stress promoted the inhibition of apoptosis and pyroptosis in vascular endothelial cells. Activation of TFEB increased autophagy and inhibited endothelial cell oxidative stress in I/R‐injured flaps. A reduction in TFEB level led to a loss of the protective effect of BF‐30, by reducing autophagy flux and increasing the accumulation of reactive oxygen species (ROS) in endothelial cells. Additionally, BF‐30 modulated TFEB activity via the AMPK–TRPML1–calcineurin signalling pathway. Conclusion and Implications BF‐30 promotes I/R‐injured skin flap survival by TFEB‐mediated up‐regulation of autophagy and inhibition of oxidative stress, which may have possible clinical applications.
科研通智能强力驱动
Strongly Powered by AbleSci AI