Effect of botulinum toxin A on vasoconstriction and sympathetic neurotransmitters in a murine random pattern skin flap model

Wound Repair and Regeneration - Tập 25 Số 1 - Trang 75-85 - 2017
Tai Suk Roh1, Bok Ki Jung1, In Sik Yun1, Dae Hyun Lew1, Young Seok Kim1,2,3
1Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
2Tel: +82 2 2019 3422
3Young Seok Kim, M.D., Ph.D. Department of Plastic & Reconstructive Surgery, Gangnam Severance Hospital, Yonsei University, College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 06273, Republic of Korea.

Tóm tắt

AbstractBlood supply is the most important factor determining the survival of a skin flap. Botulinum toxin‐A (Botox‐A) is used as pharmacologic agent not only for aesthetic purposes, but also for its vasomotor actions. This study was conducted to establish whether local application of Botox‐A increased survival of random pattern skin flaps in rats by changing the expression of neurotransmitters. Forty adult Sprague–Dawley rats with a caudally‐based random pattern skin flap were divided into two groups: Botox‐A group and saline group. Surviving flap area and cutaneous blood flow in the flap were evaluated on postoperative days 3 and 7. After injection of Botox‐A, changes in vessels were analyzed using immunohistochemical staining. Levels of norepinephrine, neuropeptide‐Y, nitric oxide, and endothelial nitric oxide synthase were analyzed quantitatively by high performance liquid chromatography, Western blot, and colorimetric assay. The survived area in the Botox‐A group was significantly higher than that in the control group on postoperative days 3 and 7. Blood flow in the Botox‐A group was significantly high in the proximal and middle areas immediately after the operation. The number of CD31‐positive vessels in the Botox‐A group was significant greater than that in the control group. Norepinephrine level in the Botox‐A group decreased significantly immediately after flap elevation and at postoperative day 3. There were no significant differences in neuropeptide‐Y level between the two groups. Nitric oxide level did not change significantly in either group despite the increase in endothelial nitric oxide synthase immediately after flap elevation and at 3 days postoperatively. In conclusion, Botox‐A increased vascular blood flow and viable flap area in rats by reducing norepinephrine level. In contrast, neuropeptide‐Y, another vasoconstrictor, was not affected by Botox‐A. Nitric oxide, a vasodilator, was also not affected by Botox‐A, despite the significant increase in endothelial nitric oxide synthase expression in the flaps.

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Tài liệu tham khảo

10.1111/j.1524-475X.2009.00477.x

10.1097/00006534-198304000-00012

10.1001/archotol.1975.00780350018004

10.1097/01.PRS.0000047404.28025.C5

10.1097/00006534-200205000-00031

10.1152/ajpheart.01253.2005

10.1002/jgm.1105

10.1111/j.1524-475X.2011.00733.x

10.1002/mds.20071

10.1016/j.jns.2005.04.017

10.1097/01.PRS.0000082208.37239.5B

10.1111/j.1524-4725.2004.30118.x

Simpson LL., 1981, The origin, structure, and pharmacological activity of botulinum toxin, Pharmacol Rev, 33, 155

10.1002/mds.20010

10.1002/mds.20066

10.1038/2280

10.1002/(SICI)1097-4598(1997)6 <146::AID-MUS10>3.0.CO;2-4

10.1136/bmj.323.7313.596

10.1212/WNL.61.9.1279

10.1097/01.prs.0000244860.00674.57

10.1097/PRS.0b013e3181a80576

10.1016/j.jhsa.2011.07.011

10.1152/ajpheart.00477.2002

Wahlestedt C, 1990, Norepinephrine and neuropeptide Y: vasoconstrictor cooperation in vivo and in vitro, Am J Physiol, 258, R736

10.1016/j.bjps.2007.12.034

10.1097/PRS.0b013e3181b989be

10.1111/dsu.12071

Vedder NB., 2006, Flap physiology

10.1097/00006534-198312000-00003

10.1097/00002508-200211001-00002

10.1016/0306-4522(87)90094-7

Kalandakanond S, 2001, Cleavage of SNAP‐25 by botulinum toxin type A requires receptor‐mediated endocytosis, pH‐dependent translocation, and zinc, J Pharmacol Exp Ther, 296, 980

10.1152/ajpheart.2001.281.5.H2124

10.1016/0896-6273(92)90104-L

10.1006/niox.2001.0376

10.1016/j.niox.2004.01.004

10.1097/01.prs.0000197214.57838.9b