Effect of natural hirudin on revascularization of ischemic skin flaps in rats by Micro-CT_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

YAN Yuyong ¹ , PAN Xinyuan ² , LIN Bojie ¹ , LIN Guanyu ¹ ,  YIN Guoqian ^1,3

1. Department of Plastic and Aesthetic Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning Guangxi, 530021, P.R.China;
2. Department of Cosmetology and Plastic Surgery Center, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning Guangxi, 530021, P.R.China;
3. Research Center for Regenerative Medicine, Guangxi Medical University, Nanning Guangxi, 530021, P.R.China;

Corresponding author：

YIN Guoqian, Email: yingq61@163.com

Keywords：

Natural hirudin; ischemic skin flap; Micro-CT; revascularization; rat

DOI：

10.7507/1002-1892.201907030

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Objective To investigate the effect of natural hirudin on revascularization of ischemic skin flap in rats using Micro-CT and three-dimensional (3D) reconstruction.Methods Thirty-two Sprague Dawley rats were prepared a ischemic skin flap (8.0 cm×1.8 cm) model on the back and randomly divided into hirudin group and control group (16 rats in each group). At immediate and within 3 days after operation, the rats were treated with hypodermic injection of natural hirudin 0.3 mL (including natural hirudin 6 ATU) every day in hirudin group and the equal amount of normal saline in control group. At 6 days after operation, the survival rate of skin flap was evaluated, histological changes were observed by HE staining, and the volemia, length of blood vessels, and number of blood vessels were analyzed with Micro-CT 3D reconstruction.Results Both groups of rats survived to the end of the experiment without infection. Different degrees of necrosis occurred in the distal part of the skin flaps in both groups at 6 days after operation, but the flap survival rate of the hirudin group (72.11%±8.97%) was significantly higher than that of control group (58.94%±4.02%) (t=3.280, P=0.008). Histological observation showed that the histological hierarchy of the hirudin group was clearer than that of the control group, with more microangiogenesis and less inflammatory response and inflammatory cell infiltration. Micro-CT 3D reconstruction showed that the flap vessels in the hirudin group were more and denser, and the volemia, length of blood vessels, and number of blood vessels were significantly higher than those in the control group (P<0.05).Conclusion Natural hirudin can reduce the inflammation of tissue, promote the regeneration and recanalization of blood vessels in ischemic skin flap, so as to improve the survival rate of the flap.

Citation： YAN Yuyong, PAN Xinyuan, LIN Bojie, LIN Guanyu, YIN Guoqian. Effect of natural hirudin on revascularization of ischemic skin flaps in rats by Micro-CT. Chinese Journal of Reparative and Reconstructive Surgery, 2020, 34(3): 382-386. doi: 10.7507/1002-1892.201907030 Copy

1.	徐永清, 范新宇. 不同皮瓣在创面修复中的应用. 中华创伤杂志, 2016, 32(4): 291-294.
2.	石磊, 陆振中, 黄旻华, 等. 局部任意皮瓣修复头皮缺损 22 例分析. 中华皮肤科杂志, 2016, 49(12): 889-890.
3.	Wang F, Peled AW, Garwood E, et al. Total skin-sparing mastectomy and immediate breast reconstruction: an evolution of technique and assessment of outcomes. Ann Surg Oncol, 2014, 21(10): 3223-3230.
4.	Lee MS, Ahmad T, Lee J, et al. Dual delivery of growth factors with coacervate-coated poly (lactic-co-glycolic acid) nanofiber improves neovascularization in a mouse skin flap model. Biomaterials, 2017, 124: 65-77.
5.	姚春丽, 张桂云, 宋嗣宏, 等. 防止任意型皮瓣坏死的相关研究进展. 中华皮肤科杂志, 2013, 46(5): 370-372.
6.	Lin R, Chen H, Callow D, et al. Multifaceted effects of astragaloside Ⅳ on promotion of random pattern skin flap survival in rats. Am J Transl Res, 2017, 9(9): 4161-4172.
7.	Wang WZ, Baynosa RC, Zamboni WA. Update on ischemia-reperfusion injury for the plastic surgeon: 2011. Plast Reconstr Surg, 2011, 128(6): 685e-692e.
8.	Douglas B, Buchholz RR. The blood circulation in pedicle flaps: an accurate test for determining its efficiency. Ann Surg, 1943, 117(5): 692-709.
9.	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.
10.	Guo-Qian Y, Gang W, Zhi-Yong S. Investigation on the microcirculation effect of local application of natural hirudin on porcine random skin flap venous congestion. Cell Biochem Biophys, 2012, 62(1): 141-146.
11.	Mao SJ, Yates MT, Owen TJ, et al. Interaction of hirudin with thrombin: identification of a minimal binding domain of hirudin that inhibits clotting activity. Biochemistry, 1988, 27(21): 8170-8173.
12.	Pan XY, Peng L, Han ZQ, et al. Hirudin promotes angiogenesis by modulating the cross-talk between p38 MAPK and ERK in rat ischemic skin flap tissue. Tissue Cell, 2015, 47(3): 301-310.
13.	张文. SkyScan 1176 Micro-CT 在骨科研究中的应用. 数字化用户, 2017, (51): 272, 266.
14.	Baird E, Taylor G. X-ray micro computed-tomography. Curr Biol, 2017, 27(8): R289-R291.
15.	McFarlane RM, Deyoung G, Henry RA. The design of a pedicle flap in the rat to study necrosis and its prevention. Plast Reconstr Surg, 1965, 35: 177-182.
16.	史广玲, 刘夕珍, 谈玲. 不同浓度肝素封管液用于 PICC 封管的效果. 中华现代护理杂志, 2011, 17(30): 3649-3650.
17.	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.
18.	Lin Y, Lin B, Lin D, et al. Effect of thymosin β4 on the survival of random skin flaps in rats. J Reconstr Microsurg, 2015, 31(6): 464-470.
19.	李国栋, 徐永清, 何晓清, 等. Tempol 对大鼠任意皮瓣成活影响的实验研究. 中国修复重建外科杂志, 2016, 30(10): 1264-1269.
20.	Erlich JH, Boyle EM, Labriola J, et al. Inhibition of the tissue factor-thrombin pathway limits infarct size after myocardial ischemia-reperfusion injury by reducing inflammation. Am J Pathol, 2000, 157(6): 1849-1862.
21.	蔡洁云, 林博杰, 潘新元, 等. 天然水蛭素联合高压氧治疗对大鼠随意皮瓣成活的影响研究. 中国修复重建外科杂志, 2018, 32(4): 484-490.
22.	Fukunaga Y, Izawa-Ishizawa Y, Horinouchi Y, et al. Topical application of nitrosonifedipine, a novel radical scavenger, ameliorates ischemic skin flap necrosis in a mouse model. Wound Repair Regen, 2017, 25(2): 217-223.
23.	Roh TS, Jung BK, Yun I, et al. Effect of botulinum toxin A on vasoconstriction and sympathetic neurotransmitters in a murine random pattern skin flap model. Wound Repair Regen, 2017, 25(1): 75-85.
24.	Rednam CK, Wilson RL, Selvaraju V, et al. Increased survivability of ischemic skin flap tissue in Flk-1. Microcirculation, 2017, 24(6). doi: 10.1111/micc.12362.
25.	韦骎兮, 殷国前, 潘新元, 等. 水蛭素对大鼠缺血皮瓣血运恢复与新生血管生成的影响. 中华医学美学美容杂志, 2016, 22(5): 300-304.
26.	Bui DT, Cordeiro PG, Hu QY, et al. Free flap reexploration: indications, treatment, and outcomes in 1193 free flaps. Plast Reconstr Surg, 2007, 119(7): 2092-2100.
27.	袁相斌, 陈卫平, 杨勇, 等. 随意超薄皮瓣的超薄层次及长宽比例的实验研究. 中国修复重建外科杂志, 1994, 8(2): 71-73.
28.	王家瑞, 刘达恩, 农庆文, 等. 肝细胞生长因子对大鼠背部超长任意皮瓣存活率影响的实验研究. 中国美容医学, 2011, 20(3): 430-433.
29.	蔡俊, 蒋树林. 心肌组织工程血管化策略的研究进展. 疑难病杂志, 2016, 15(12): 1309-1312, 1317.
30.	郝艳丽, 刘蓉, 韩伟, 等. 水蛭素的给药途径及其相关剂型研究进展. 中国新药杂志, 2007, 16(8): 595-599.

1. 徐永清, 范新宇. 不同皮瓣在创面修复中的应用. 中华创伤杂志, 2016, 32(4): 291-294.
2. 石磊, 陆振中, 黄旻华, 等. 局部任意皮瓣修复头皮缺损 22 例分析. 中华皮肤科杂志, 2016, 49(12): 889-890.
3. Wang F, Peled AW, Garwood E, et al. Total skin-sparing mastectomy and immediate breast reconstruction: an evolution of technique and assessment of outcomes. Ann Surg Oncol, 2014, 21(10): 3223-3230.
4. Lee MS, Ahmad T, Lee J, et al. Dual delivery of growth factors with coacervate-coated poly (lactic-co-glycolic acid) nanofiber improves neovascularization in a mouse skin flap model. Biomaterials, 2017, 124: 65-77.
5. 姚春丽, 张桂云, 宋嗣宏, 等. 防止任意型皮瓣坏死的相关研究进展. 中华皮肤科杂志, 2013, 46(5): 370-372.
6. Lin R, Chen H, Callow D, et al. Multifaceted effects of astragaloside Ⅳ on promotion of random pattern skin flap survival in rats. Am J Transl Res, 2017, 9(9): 4161-4172.
7. Wang WZ, Baynosa RC, Zamboni WA. Update on ischemia-reperfusion injury for the plastic surgeon: 2011. Plast Reconstr Surg, 2011, 128(6): 685e-692e.
8. Douglas B, Buchholz RR. The blood circulation in pedicle flaps: an accurate test for determining its efficiency. Ann Surg, 1943, 117(5): 692-709.
9. 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.
10. Guo-Qian Y, Gang W, Zhi-Yong S. Investigation on the microcirculation effect of local application of natural hirudin on porcine random skin flap venous congestion. Cell Biochem Biophys, 2012, 62(1): 141-146.
11. Mao SJ, Yates MT, Owen TJ, et al. Interaction of hirudin with thrombin: identification of a minimal binding domain of hirudin that inhibits clotting activity. Biochemistry, 1988, 27(21): 8170-8173.
12. Pan XY, Peng L, Han ZQ, et al. Hirudin promotes angiogenesis by modulating the cross-talk between p38 MAPK and ERK in rat ischemic skin flap tissue. Tissue Cell, 2015, 47(3): 301-310.
13. 张文. SkyScan 1176 Micro-CT 在骨科研究中的应用. 数字化用户, 2017, (51): 272, 266.
14. Baird E, Taylor G. X-ray micro computed-tomography. Curr Biol, 2017, 27(8): R289-R291.
15. McFarlane RM, Deyoung G, Henry RA. The design of a pedicle flap in the rat to study necrosis and its prevention. Plast Reconstr Surg, 1965, 35: 177-182.
16. 史广玲, 刘夕珍, 谈玲. 不同浓度肝素封管液用于 PICC 封管的效果. 中华现代护理杂志, 2011, 17(30): 3649-3650.
17. 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.
18. Lin Y, Lin B, Lin D, et al. Effect of thymosin β4 on the survival of random skin flaps in rats. J Reconstr Microsurg, 2015, 31(6): 464-470.
19. 李国栋, 徐永清, 何晓清, 等. Tempol 对大鼠任意皮瓣成活影响的实验研究. 中国修复重建外科杂志, 2016, 30(10): 1264-1269.
20. Erlich JH, Boyle EM, Labriola J, et al. Inhibition of the tissue factor-thrombin pathway limits infarct size after myocardial ischemia-reperfusion injury by reducing inflammation. Am J Pathol, 2000, 157(6): 1849-1862.
21. 蔡洁云, 林博杰, 潘新元, 等. 天然水蛭素联合高压氧治疗对大鼠随意皮瓣成活的影响研究. 中国修复重建外科杂志, 2018, 32(4): 484-490.
22. Fukunaga Y, Izawa-Ishizawa Y, Horinouchi Y, et al. Topical application of nitrosonifedipine, a novel radical scavenger, ameliorates ischemic skin flap necrosis in a mouse model. Wound Repair Regen, 2017, 25(2): 217-223.
23. Roh TS, Jung BK, Yun I, et al. Effect of botulinum toxin A on vasoconstriction and sympathetic neurotransmitters in a murine random pattern skin flap model. Wound Repair Regen, 2017, 25(1): 75-85.
24. Rednam CK, Wilson RL, Selvaraju V, et al. Increased survivability of ischemic skin flap tissue in Flk-1. Microcirculation, 2017, 24(6). doi: 10.1111/micc.12362.
25. 韦骎兮, 殷国前, 潘新元, 等. 水蛭素对大鼠缺血皮瓣血运恢复与新生血管生成的影响. 中华医学美学美容杂志, 2016, 22(5): 300-304.
26. Bui DT, Cordeiro PG, Hu QY, et al. Free flap reexploration: indications, treatment, and outcomes in 1193 free flaps. Plast Reconstr Surg, 2007, 119(7): 2092-2100.
27. 袁相斌, 陈卫平, 杨勇, 等. 随意超薄皮瓣的超薄层次及长宽比例的实验研究. 中国修复重建外科杂志, 1994, 8(2): 71-73.
28. 王家瑞, 刘达恩, 农庆文, 等. 肝细胞生长因子对大鼠背部超长任意皮瓣存活率影响的实验研究. 中国美容医学, 2011, 20(3): 430-433.
29. 蔡俊, 蒋树林. 心肌组织工程血管化策略的研究进展. 疑难病杂志, 2016, 15(12): 1309-1312, 1317.
30. 郝艳丽, 刘蓉, 韩伟, 等. 水蛭素的给药途径及其相关剂型研究进展. 中国新药杂志, 2007, 16(8): 595-599.

Chinese Journal of Reparative and Reconstructive Surgery

Effect of natural hirudin on revascularization of ischemic skin flaps in rats by Micro-CT

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