Dataset Information

Salvianolic Acid B Promotes the Survival of Random-Pattern Skin Flaps in Rats by Inducing Autophagy.

ABSTRACT: Random-pattern skin flap transplantation is frequently applied in plastic and reconstructive surgery. However, the distal part of the flap often suffers necrosis due to ischemia. In this study, the effects of salvianolic acid B (Sal B) on flap survival were evaluated, and the underlying mechanisms were investigated. Sal B improved the survival area, reduced tissue edema, and increased the number of microvessels in skin flaps after 7 days, whereas an autophagy inhibitor (3-methyladenine) reversed the Sal B-induced increase in flap viability. In addition, Sal B stimulated angiogenesis, inhibited apoptosis, reduced oxidative stress, and upregulated autophagy in areas of ischemia. Moreover, the effects of Sal B on angiogenesis, apoptosis, and oxidative stress were reversed by autophagy inhibition. Overall, our findings suggest that Sal B has pro-angiogenesis, anti-apoptosis, and anti-oxidative stress effects by stimulating autophagy, which enhances the survival of random-pattern skin flaps.

SUBMITTER: Lin J

PROVIDER: S-EPMC6206168 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Salvianolic Acid B Promotes the Survival of Random-Pattern Skin Flaps in Rats by Inducing Autophagy.

Lin Jinti J Lin Renjin R Li Shihen S Wu Hongqiang H Ding Jian J Xiang Guangheng G Li Shi S Wang Yiru Y Lin Dingsheng D Gao Weiyang W Kong Jianzhong J Xu Huazi H Zhou Kailiang K

Frontiers in pharmacology 20181023

Random-pattern skin flap transplantation is frequently applied in plastic and reconstructive surgery. However, the distal part of the flap often suffers necrosis due to ischemia. In this study, the effects of salvianolic acid B (Sal B) on flap survival were evaluated, and the underlying mechanisms were investigated. Sal B improved the survival area, reduced tissue edema, and increased the number of microvessels in skin flaps after 7 days, whereas an autophagy inhibitor (3-methyladenine) reversed ...[more]

PMID: 30405410

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Project description:Necrosis that appears at the ischemic distal end of random-pattern skin flaps increases the pain and economic burden of patients. Necroptosis is thought to contribute to flap necrosis. Lysosomal membrane permeabilization (LMP) plays an indispensable role in the regulation of necroptosis. Nonetheless, the mechanisms by which lysosomal membranes become leaky and the relationship between necroptosis and lysosomes are still unclear in ischemic flaps. Based on Western blotting, immunofluorescence, enzyme-linked immunosorbent assay, and liquid chromatography-mass spectrometry (LC-MS) analysis results, we found that LMP was presented in the ischemic distal portion of random-pattern skin flaps, which leads to disruption of lysosomal function and macroautophagic/autophagic flux, increased necroptosis, and aggravated necrosis of the ischemic flaps. Moreover, bioinformatics analysis of the LC-MS results enabled us to focus on the role of PLA2G4E/cPLA2 (phospholipase A2, group IVE) in LMP of the ischemic flaps. In vivo inhibition of PLA2G4E with an adeno-associated virus vector attenuated LMP and necroptosis, and promoted flap survival. In addition, microRNA-seq helped us determine that Mir504-5p was differentially expressed in ischemic flaps. A string of in vitro and in vivo tests was employed to verify the inhibitory effect of Mir504-5p on PLA2G4E, LMP and necroptosis. Finally, we concluded that the inhibition of PLA2G4E by Mir504-5p reduced LMP-induced necroptosis, thereby promoting the survival of random-pattern skin flaps.Abbreviations: AAV: adeno-associated virus; ACTA2/α;-SMA: actin alpha 2, smooth muscle, aorta; ALOX15/12/15-LOX: arachidonate 15- lipoxygenase; c-CASP8: cleaved caspase; c-CASP3: cleaved caspase 3; CTSD: cathepsin D; CTSB: cathepsin B; CTSL: cathepsin L; DMECs: primary mouse dermal microvascular endothelial cells; ELISA: enzyme-linked immunosorbent assay; F-CHP: 5-FAM-conjugated collagen hybridizing peptide; FISH: fluorescence in situ hybridization; HUVECs: human umbilical vein endothelial cells; LAMP1: lysosomal-associated membrane protein 1; LAMP2: lysosomal-associated membrane protein 2; LC-MS: liquid chromatography-mass spectrometry; LDBF: laser doppler blood flow; LMP: lysosomal membrane permeabilization; LPE: lysophosphatidylethanolamine; LPC: lysophosphatidylcholine; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MLKL: mixed lineage kinase domain-like; NDI: N-dodecylimidazole; PECAM1/CD31: platelet/endothelial cell adhesion molecule 1; PLA2G4A/cPLA2: phospholipase A2, group IVA (cytosolic, calcium-dependent); PLA2G4E/cPLA2: phospholipase A2, group IVE; qPCR: quantitative real-time polymerase chain reaction; RIPK1: receptor (TNFRSF)-interacting serine-threonine kinase 1; RIPK3: receptor-interacting serine-threonine kinase 3; RISC: RNA-induced silencing complex; ROS: reactive oxygen species; shRNA: short hairpin RNA; SQSTM1: sequestosome 1; TBHP: tert-butyl hydroperoxide; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labelling.

Dataset Information

Salvianolic Acid B Promotes the Survival of Random-Pattern Skin Flaps in Rats by Inducing Autophagy.

Publications

Salvianolic Acid B Promotes the Survival of Random-Pattern Skin Flaps in Rats by Inducing Autophagy.

Similar Datasets

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