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. 不同皮瓣在創面修復中的應用. 中華創傷雜志, 2016, 32(4): 291-294.
2.	石磊, 陸振中, 黃旻華, 等. 局部任意皮瓣修復頭皮缺損 22 例分析. 中華皮膚科雜志, 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.	姚春麗, 張桂云, 宋嗣宏, 等. 防止任意型皮瓣壞死的相關研究進展. 中華皮膚科雜志, 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.	韓志強, 殷國前, 韋淑怡, 等. 天然水蛭素對大鼠背部隨意皮瓣早期斷蒂后成活的影響. 中國修復重建外科雜志, 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.	張文. SkyScan 1176 Micro-CT 在骨科研究中的應用. 數字化用戶, 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.	史廣玲, 劉夕珍, 談玲. 不同濃度肝素封管液用于 PICC 封管的效果. 中華現代護理雜志, 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.	李國棟, 徐永清, 何曉清, 等. Tempol 對大鼠任意皮瓣成活影響的實驗研究. 中國修復重建外科雜志, 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.	蔡潔云, 林博杰, 潘新元, 等. 天然水蛭素聯合高壓氧治療對大鼠隨意皮瓣成活的影響研究. 中國修復重建外科雜志, 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.	韋骎兮, 殷國前, 潘新元, 等. 水蛭素對大鼠缺血皮瓣血運恢復與新生血管生成的影響. 中華醫學美學美容雜志, 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, 陳衛平, 楊勇, 等. 隨意超薄皮瓣的超薄層次及長寬比例的實驗研究. 中國修復重建外科雜志, 1994, 8(2): 71-73.
28.	王家瑞, 劉達恩, 農慶文, 等. 肝細胞生長因子對大鼠背部超長任意皮瓣存活率影響的實驗研究. 中國美容醫學, 2011, 20(3): 430-433.
29.	蔡俊, 蔣樹林. 心肌組織工程血管化策略的研究進展. 疑難病雜志, 2016, 15(12): 1309-1312, 1317.
30.	郝艷麗, 劉蓉, 韓偉, 等. 水蛭素的給藥途徑及其相關劑型研究進展. 中國新藥雜志, 2007, 16(8): 595-599.

1. 徐永清, 范新宇. 不同皮瓣在創面修復中的應用. 中華創傷雜志, 2016, 32(4): 291-294.
2. 石磊, 陸振中, 黃旻華, 等. 局部任意皮瓣修復頭皮缺損 22 例分析. 中華皮膚科雜志, 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. 姚春麗, 張桂云, 宋嗣宏, 等. 防止任意型皮瓣壞死的相關研究進展. 中華皮膚科雜志, 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. 韓志強, 殷國前, 韋淑怡, 等. 天然水蛭素對大鼠背部隨意皮瓣早期斷蒂后成活的影響. 中國修復重建外科雜志, 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. 張文. SkyScan 1176 Micro-CT 在骨科研究中的應用. 數字化用戶, 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. 史廣玲, 劉夕珍, 談玲. 不同濃度肝素封管液用于 PICC 封管的效果. 中華現代護理雜志, 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. 李國棟, 徐永清, 何曉清, 等. Tempol 對大鼠任意皮瓣成活影響的實驗研究. 中國修復重建外科雜志, 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. 蔡潔云, 林博杰, 潘新元, 等. 天然水蛭素聯合高壓氧治療對大鼠隨意皮瓣成活的影響研究. 中國修復重建外科雜志, 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. 韋骎兮, 殷國前, 潘新元, 等. 水蛭素對大鼠缺血皮瓣血運恢復與新生血管生成的影響. 中華醫學美學美容雜志, 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, 陳衛平, 楊勇, 等. 隨意超薄皮瓣的超薄層次及長寬比例的實驗研究. 中國修復重建外科雜志, 1994, 8(2): 71-73.
28. 王家瑞, 劉達恩, 農慶文, 等. 肝細胞生長因子對大鼠背部超長任意皮瓣存活率影響的實驗研究. 中國美容醫學, 2011, 20(3): 430-433.
29. 蔡俊, 蔣樹林. 心肌組織工程血管化策略的研究進展. 疑難病雜志, 2016, 15(12): 1309-1312, 1317.
30. 郝艷麗, 劉蓉, 韓偉, 等. 水蛭素的給藥途徑及其相關劑型研究進展. 中國新藥雜志, 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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