Therapeutic potential of pravastatin for random skin flaps necrosis: involvement of promoting angiogenesis and inhibiting apoptosis and oxidative stress

Abstract

Background:

Random skin flap is frequently used in plastic and reconstructive surgery, but its distal part often occurs ischemia and necrosis. Pravastatin (Prava) with bioactivities of pro-angiogenesis, anti-apoptosis and anti-oxidative stress, may be beneficial for flap survival.

Materials and methods:

A modified McFarlane flap model was performed in Sprague-Dawley rats. The animals were divided into the Control and Prava groups and treated as follows: the Prava group was injected intraperitoneally with 2 mg/kg Prava for consecutive 7 days, and the Control group received an equal volume of vehicle daily. On day 7, the necrosis skin flaps were observed, while visualization of blood flow below the tissue surface was performed by Laser Doppler blood flow imaging (LDBFI). Then animals were euthanized, and levels of angiogenesis, apoptosis and oxidative stress were analyzed.

Results:

Prava decreased necrosis and edema of skin flaps compared with the Control group, with more blood flow in the flap under LDBFI. Prava treatment increased the mean vessels density, elevated the expression levels of angiogenic proteins (matrix metallopeptidase 9, vascular endothelial growth factor, Cadherin5) and antioxidant proteins (superoxide dismutase 1 (SOD1), endothelial nitric oxide synthase, heme oxygenase), and decreased the expression of apoptotic factors (BAX, CYC, Caspase3). In addition, malondialdehyde content was reduced, and glutathione level and SOD activity were increased in the skin flaps after treatment with Prava.

Conclusion:

Prava promotes survival of random skin flap through induction of angiogenesis, and inhibition of apoptosis and oxidative stress.

Keywords:

• Pravastatin
• random skin flap
• angiogenesis
• oxidative stress
• apoptosis

View correction statement:

Therapeutic potential of pravastatin for random skin flaps necrosis: involvement of promoting angiogenesis and inhibiting apoptosis and oxidative stress [Corrigendum]

Acknowledgments

This work was supported by grants from Natural Science Foundation of China (No. 81601705 to Kailiang Zhou, No. 81572227, No. 81873992 to Huazi Xu, No. 81701828 to Yijie Chen); Natural Science Foundation of Zhejiang Province (No. LQ18C010003 to Chang Jia, No. LY16H180008 to Yijie Chen); Zhejiang Provincial Medicine and Health Technology Project (No. 2017KY472 to Kailiang Zhou); Wenzhou Science and Technology Bureau Foundation (Y20150082 to Yijie Chen). Huzhou Science and Technology Bureau Foundation (2018GYB42 to Yongli Wang).

Consent for publication

Hereby we declare that our institutes are aware of the work and declare consent for publication of the manuscript. We received consent to publish the animal experimental data from the animal ethical committee.

Availability of data and materials

All the data are presented in the paper.

Author contributions

Jinti Lin and Chang Jia wrote the manuscript. Jinti Lin, Yongli Wang, and Shanghong Jiang prepared figures and collected samples. Zhenyu Jia, Nan Chen, Shimin Sheng, and Shihen Li analyzed data, Chang Jia, Kailiang Zhou, and Yijie Chen designed the experiments. Liangfu Jiang, Huazi Xu, Kailiang Zhou, and Yijie Chen revised the manuscript. All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.