EFFECTS OF Tempol ON SURVIVAL OF RANDOM PATTERN SKIN FLAPS IN RATS_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LIGuodong ¹ ,  XUYongqing ² , HEXiaoqing ² , YANGFan ³ , CHENDewei ³ , LUOHaotian ² , YANGXi ¹

1. Brigade of Postgraduate Managementy, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, 400038, P. R. China;
2. Department of Orthopedics, Kunming General Hospitaly, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, 400038, P. R. China;
3. Department of Pathophysiology and High Altitude Pathology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, 400038, P. R. China;

Corresponding author：

XUYongqing, Email: xuyongqingkm@163.net

Keywords：

Tempol; Long random pattern skin flap; Vasculogenesis; Oxidative stress; Inflammation reaction; Rat

DOI：

10.7507/1002-1892.20160258

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Objective To study the effects of the new small molecular oxygen free radical scavenger Tempol on the survival and vasculogenesis of the long random pattern skin flap (LRPSF) and its mechanism. Methods Eighty-four male Sprague Dawley rats were randomly divided into control and Tempol groups (42 rats in each group). LRPSF of 9 cm×3 cm in size were prepared on the backs of rats in two groups based on the Mcfarlane flap. Rats were administered with Tempol (100 mg/kg) in the Tempol group and with normal saline in the control group by intraperitoneal injection at 15 minutes before operation and at 1-7 day after operation. The rat and the skin flap survival conditions were observed after operation; the survival rate of skin flap was measured, and the vascular structure, vascular volume, and total length of blood vessels were analyzed with Micro-CT three-dimensional imaging after 7 days; HE staining was used to observe the structure of the skin flaps and inflammation, immumohistochemical staining to observe vascular endothelial growth factor (VEGF) expression; water-soluble tetrazolium-1 method was used to measure the content of superoxide dismutase (SOD) and malondialdehyde (MDA), and ELISA to detect the expressions of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) after 1, 3, and 7 days. Results All of rats survived after operation, without hemorrhage, edema, and infection. With the extension of time, necrosis occurred in the distal part of the skin flaps in 2 groups, but the necrosis degree of the Tempol group was lower than that of control group; meanwhile, the blood vessel distribution and continuity were better than those of control group. The skin flaps survival rate, vascular volume, and total length of blood vessels of Tempol group were significantly higher than those of control group after 7 days (P<0.05). The clearer skin flaps structure, lighter inflammation reaction and inflammation cell infiltration, and higher VEGF staining intensity were observed in the Tempol group than the control group after 7 days. There was no significant difference in SOD, MDA, and TNF-α, and IL-6 contents between the 2 groups at immediate after operation. SOD significantly increased, but MDA, TNF-α, and IL-6 contents significantly decreased in the Tempol group when compared with control group after 1, 3, and 7 days (P<0.05). Conclusion Tempol can significantly promote the LRPSF survival rates, its mechanism is closely related to the promotion of vasculogenesis and reduction of oxidative stress and inflammation.

Citation： LI Guodong, XU Yongqing, HE Xiaoqing, YANG Fan, CHEN Dewei, LUO Haotian, YANG Xi. EFFECTS OF Tempol ON SURVIVAL OF RANDOM PATTERN SKIN FLAPS IN RATS. Chinese Journal of Reparative and Reconstructive Surgery, 2016, 30(10): 1264-1269. doi: 10.7507/1002-1892.20160258 Copy

1.	Weng W, Zhang F, Lineaweaver WC, et al. The value of postconditioning in plastic and reconstructive surgery:A systematic review. J Reconstr Microsurg, 2016, 32(4):285-293.
2.	Vorobjeva NV, Pinegin BV. Effects of the antioxidants Trolox, Tiron and Tempol on neutrophil extracellular trap formation. Immunobiology, 2016, 221(2):208-219.
3.	Zhu J, Rebecchi MJ, Wang Q, et al. Chronic Tempol treatment restores pharmacological preconditioning in the senescent rat heart. Am J Physiol Heart Circ Physiol, 2013, 304(5):H649-H659.
4.	Quan HH, Kang KS, Sohn YK, et al. Tempol reduces injury area in rat model of spinal cord contusion injury through suppression of iNOS and COX-2 expression. Neurol Sci, 2013, 34(9):1621-1628.
5.	Wilcox CS, Pearlman A. Chemistry and antihypertensive effects of tempol and other nitroxides. Pharmacol Rev, 2008, 60(4):418-469.
6.	Briggs PC. The McFarlane flap. Plast Reconstr Surg, 1987, 80(3):472-473.
7.	Wang Y, Chen SY, Gao WY, et al. Experimental study of survival of pedicled perforator flap with flow-through and flow-end blood supply. Br J Surg, 2015, 102(4):375-381.
8.	Kailiang Z, Yihui Z, Dingsheng L, et al. Effects of muscone on random skin flap survival in rats. J Reconstr Microsurg, 2016, 32(3):200-207.
9.	Zhou KL, Zhang YH, Lin DS, et al. Effects of calcitriol on random skin flap survival in rats. Sci Rep, 2016, 6:18945.
10.	沈美华, 任鹏, 肖虎, 等. 基于CT血管造影的胸背动脉三维可视化研究. 中国修复重建外科杂志, 2015, 29(3):326-330.
11.	Zhang Y, Xu H, Wang T, et al. Remote limb ischemic post-conditioning attenuates ischemia-reperfusion injury in rat skin flap by limiting oxidative stress. Acta Cir Bras, 2016, 31(1):15-21.
12.	韩志强, 殷国前, 韦淑怡, 等. 天然水蛭素对大鼠背部随意皮瓣早期断蒂后成活的影响. 中国修复重建外科杂志, 2013, 27(6):738-742.
13.	Kim HJ, Xu L, Chang KC, et al. Anti-inflammatory effects of anthocyanins from black soybean seed coat on the keratinocytes and ischemia-reperfusion injury in rat skin flaps. Microsurgery, 2012, 32(7):563-570.
14.	Wanyong Y, Zefeng T, Xiufeng X, et al. Tempol alleviates intracerebral hemorrhage-induced brain injury possibly by attenuating nitrative stress. Neuroreport, 2015, 26(14):842-849.
15.	Vourtsis SA, Spyriounis PK, Agrogiannis GD, et al. VEGF application on rat skin flap survival. J Invest Surg, 2012, 25(1):14-19.
16.	Basu G, Downey H, Guo S, et al. Prevention of distal flap necrosis in a rat random skin flap model by gene electrotransfer delivering VEGF(165) plasmid. J Gene Med, 2014, 16(3-4):55-65.
17.	Silva JJ, Pompeu DG, Ximenes NC, et al. Effects of kaurenoic acid and arginine on random skin flap oxidative stress, inflammation, and cytokines in rats. Aesthetic Plast Surg, 2015, 39(6):971-977.
18.	Pirc ET, Modec B, Cer-Kerčmar K, et al. Synthesis, structure, antioxidant and SOD-mimetic activity of[Cu(xanthurenate)(nicotinamide)(H2O)] complexes. Monatshefte für Chemie-Chemical Monthly, 2014, 145(6):911-920.
19.	Koh YH, Park YS, Takahashi M, et al. Aldehyde reductase gene expression by lipid peroxidation end products, MDA and HNE. Free Radic Res, 2000, 33(6):739-746.
20.	Tsai TC, Tung YT, Kuo YH, et al. Anti-inflammatory effects of Antrodia camphorata, a herbal medicine, in a mouse skin ischemia model. J Ethnopharmacol, 2015, 159(1):113-121.
21.	Zhang M, Zhou J, Wang L, et al. Caffeic acid reduces cutaneous tumor necrosis factor Alpha (TNF-α), IL-6 and IL-1β levels and ameliorates skin edema in acute and chronic model of cutaneous inflammation in mice. Biol Pharm Bull, 2014, 37(3):347-354.

1. Weng W, Zhang F, Lineaweaver WC, et al. The value of postconditioning in plastic and reconstructive surgery:A systematic review. J Reconstr Microsurg, 2016, 32(4):285-293.
2. Vorobjeva NV, Pinegin BV. Effects of the antioxidants Trolox, Tiron and Tempol on neutrophil extracellular trap formation. Immunobiology, 2016, 221(2):208-219.
3. Zhu J, Rebecchi MJ, Wang Q, et al. Chronic Tempol treatment restores pharmacological preconditioning in the senescent rat heart. Am J Physiol Heart Circ Physiol, 2013, 304(5):H649-H659.
4. Quan HH, Kang KS, Sohn YK, et al. Tempol reduces injury area in rat model of spinal cord contusion injury through suppression of iNOS and COX-2 expression. Neurol Sci, 2013, 34(9):1621-1628.
5. Wilcox CS, Pearlman A. Chemistry and antihypertensive effects of tempol and other nitroxides. Pharmacol Rev, 2008, 60(4):418-469.
6. Briggs PC. The McFarlane flap. Plast Reconstr Surg, 1987, 80(3):472-473.
7. Wang Y, Chen SY, Gao WY, et al. Experimental study of survival of pedicled perforator flap with flow-through and flow-end blood supply. Br J Surg, 2015, 102(4):375-381.
8. Kailiang Z, Yihui Z, Dingsheng L, et al. Effects of muscone on random skin flap survival in rats. J Reconstr Microsurg, 2016, 32(3):200-207.
9. Zhou KL, Zhang YH, Lin DS, et al. Effects of calcitriol on random skin flap survival in rats. Sci Rep, 2016, 6:18945.
10. 沈美华, 任鹏, 肖虎, 等. 基于CT血管造影的胸背动脉三维可视化研究. 中国修复重建外科杂志, 2015, 29(3):326-330.
11. Zhang Y, Xu H, Wang T, et al. Remote limb ischemic post-conditioning attenuates ischemia-reperfusion injury in rat skin flap by limiting oxidative stress. Acta Cir Bras, 2016, 31(1):15-21.
12. 韩志强, 殷国前, 韦淑怡, 等. 天然水蛭素对大鼠背部随意皮瓣早期断蒂后成活的影响. 中国修复重建外科杂志, 2013, 27(6):738-742.
13. Kim HJ, Xu L, Chang KC, et al. Anti-inflammatory effects of anthocyanins from black soybean seed coat on the keratinocytes and ischemia-reperfusion injury in rat skin flaps. Microsurgery, 2012, 32(7):563-570.
14. Wanyong Y, Zefeng T, Xiufeng X, et al. Tempol alleviates intracerebral hemorrhage-induced brain injury possibly by attenuating nitrative stress. Neuroreport, 2015, 26(14):842-849.
15. Vourtsis SA, Spyriounis PK, Agrogiannis GD, et al. VEGF application on rat skin flap survival. J Invest Surg, 2012, 25(1):14-19.
16. Basu G, Downey H, Guo S, et al. Prevention of distal flap necrosis in a rat random skin flap model by gene electrotransfer delivering VEGF(165) plasmid. J Gene Med, 2014, 16(3-4):55-65.
17. Silva JJ, Pompeu DG, Ximenes NC, et al. Effects of kaurenoic acid and arginine on random skin flap oxidative stress, inflammation, and cytokines in rats. Aesthetic Plast Surg, 2015, 39(6):971-977.
18. Pirc ET, Modec B, Cer-Kerčmar K, et al. Synthesis, structure, antioxidant and SOD-mimetic activity of[Cu(xanthurenate)(nicotinamide)(H2O)] complexes. Monatshefte für Chemie-Chemical Monthly, 2014, 145(6):911-920.
19. Koh YH, Park YS, Takahashi M, et al. Aldehyde reductase gene expression by lipid peroxidation end products, MDA and HNE. Free Radic Res, 2000, 33(6):739-746.
20. Tsai TC, Tung YT, Kuo YH, et al. Anti-inflammatory effects of Antrodia camphorata, a herbal medicine, in a mouse skin ischemia model. J Ethnopharmacol, 2015, 159(1):113-121.
21. Zhang M, Zhou J, Wang L, et al. Caffeic acid reduces cutaneous tumor necrosis factor Alpha (TNF-α), IL-6 and IL-1β levels and ameliorates skin edema in acute and chronic model of cutaneous inflammation in mice. Biol Pharm Bull, 2014, 37(3):347-354.

Chinese Journal of Reparative and Reconstructive Surgery

EFFECTS OF Tempol ON SURVIVAL OF RANDOM PATTERN SKIN FLAPS IN RATS

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