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Am J Transl Res. 2017 Aug 15;9(8):3642-3653. eCollection 2017.

Calcitriol promotes survival of experimental random pattern flap via activation of autophagy.

American journal of translational research

Long Chen, Kailiang Zhou, Huanwen Chen, Shihen Li, Dingsheng Lin, Dongsheng Zhou

Affiliations

  1. Department of Traumatic Orthopedics, Shandong Provincial Hospital, Shandong University324 Jin Wu Wei Seventh Road, Jinan 250021, Shandong, China.
  2. Department of Orthopedics, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University109 W Xueyuan Road, Wenzhou 325000, Zhejiang, China.
  3. University of Maryland School of Medicine10 S Pine Street, Baltimore, MD 21201, USA.

PMID: 28861155 PMCID: PMC5575178

Abstract

Calcitriol can promote random pattern flap survival and increase autophagy activity. However, effect of autophagy on flap survival after calcitriol treatment, along with the underlying mechanism, is undefined. In this study, the "McFarlane flap" model was established in 72 rats divided into control, calcitriol, and calcitriol+3-methyladenine (3MA) groups and injected with saline, calcitriol, and calcitriol plus 3MA, respectively. The percentage flap survival area and tissue water content were tested after 7 days. The extent of autophagy was evaluated by the expression of the autophagy markers LC3-II/I, Beclin1, and p62. Flap angiogenesis was assessed via hematoxylin and eosin (H&E) staining and immunohistochemistry (for CD34 levels). The level of vascular endothelial growth factor (VEGF) protein/mRNA was measured. Oxidative stress was assessed by measuring the activity of tissue superoxide dismutase (SOD) and the contents of glutathione (GSH) and malondialdehyde (MDA). Our results showed that 3MA decreased autophagy in random skin flap treated with calcitriol. Compared with the calcitriol group, the calcitriol+3MA group showed a smaller mean flap survival area and greater tissue edema, had a markedly decreased level of VEGF mRNA/protein and SOD activity, and a significantly higher level of MDA and GSH. H&E staining and immunohistochemistry showed that angiogenesis was inhibited in this group. In conclusion, calcitriol increased angiogenesis and reduced oxidative stress via activation of autophagy, contributing to a significant increase in random skin flap survival.

Keywords: Calcitriol; angiopoiesis; autophagy; oxidative stress; random pattern flap survival

Conflict of interest statement

None.

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