DOXORUBICIN PRECONDITIONING INSTEAD OF ISCHEMIC PRECONDITIONING IN PROVIDING ISCHEMIC TOLERANCE FOR RATS ABDOMEN ISLAND FLAPS_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LI Hong ¹ , CEN Ying ² , ZHANG Zhenyu ²

1Department of Burns and Plastic Surgery, the Second People’s Hospital of Chengdu, Chengdu Sichuan, 610017, P.R.China;;
2Department of Burns and Plastic Surgery, West China Hospital, Sichuan University. Corresponding author: CEN Ying, E-mail: cenying0141@163.com;

Corresponding author：

Keywords：

Doxorubicin; Ischemia/reperfusion injury of flap Ischemic preconditioning; Rat

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Objective To investigate the effects and mechanism of doxorubicin preconditioning in providing ischemic tolerance for rats abdomen island flaps. Methods Twenty-four healthy adult Sprague Dawley rats, 12 males and 12 females, were randomly divided into 3 groups (n=8): control group (group A), ischemic preconditioning group (group B), and doxorubicin preconditioning group (group C). After the abdomen island flap (6 cm × 3 cm in size) based on the superficial inferior epigastric neurovascular bundle was prepared, group A had no further treatment; group B was given a 10-minute ischemia followed by a 10-minute reperfusion for 4 times; and group C was given pretreatment with doxorubicin (1 mg/kg) by injection of the inferior epigastric vein. After 24 hours, the inferior epigastric vessels were blocked by vascular clamp for 4 hours, followed by reperfusion 2 hours to prepare ischemia/reperfusion (I/R) injury model. The rat survival was observed after operation; at 0, 8, 12, 24, and 30 hours after I/R injury, the malonyldiadehyde (MDA) and superoxide dismutase (SOD) levels were measured. At 7 days after I/R injury, the survival rate of flap were calculated and the flaps were harvested for histological observation. Results During experiment, 5 rats died (1 rat in groups A and B respectively, 3 rats in group C) and were added. The survival rates of the flap in group A (10.10% ± 0.43%) was lower than those in group B (91.63% ± 1.76%) and in group C (92.75% ± 1.48%) at 7 days after I/R injury, showing significant differences (P lt; 0.05), and there was no significant difference between groups B and C (t=0.29, P=0.77). Significant difference was found in MDA level and SOD level between group A and groups B, C after 8 hours (P lt; 0.05), and there was no significant difference between groups B and C (P gt; 0.05). Histological observation showed that inflammatory cells infiltration was more obvious and hyperplasia of fibers was weaker in group A than in groups B and C. Conclusion Doxorubicin preconditioning can provide ischemic tolerance for rats abdomen island flaps and protect flaps from the I/R injury. The possible mechanism may be related to that doxorubicin can induce endogenous protections.

Citation： LI Hong,CEN Ying,ZHANG Zhenyu. DOXORUBICIN PRECONDITIONING INSTEAD OF ISCHEMIC PRECONDITIONING IN PROVIDING ISCHEMIC TOLERANCE FOR RATS ABDOMEN ISLAND FLAPS. Chinese Journal of Reparative and Reconstructive Surgery, 2012, 26(12): 1501-1504. doi: Copy

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2.	Hellström PM. Vagotomy inhibits the effect of neurotensin on gastrointestinal transit in the rat. Acta Physiol Scand, 1986, 128(1): 47-55.
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4.	吴刚, 刘永锋, 杨蕾, 等. 阿霉素预处理替代缺血预处理提供鼠肝缺血耐受力的实验研究. 中华肝胆外科杂志, 2002, 8(5): 297-299.
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7.	吴升华, 杨运昌, 王兆铭. 阿霉素心脏毒性中脂质过氧化的研究. 中国抗生素杂志, 1989, 14(5): 349-354.
8.	吴立春, 陈国桢, 方中良. 热休克蛋白与心肌缺血预适应延迟保护作用的关系. 医学综述, 2008, 8(15): 2252-2254.
9.	屈新才, 王继亮, 秦涛, 等. 供肝缺血预处理对大鼠肝移植缺血再灌注损伤的保护性作用. 中国普通外科杂志, 2007, 16(3): 240-244.
10.	汪晓筠, 谢智, 王建新, 等. 热休克联合缺血预处理对大鼠心肌缺血再灌注损伤早期的保护作用研究. 实用医学杂志, 2012, 28(5): 711-714.
11.	徐久宏, 张三典, 高耀明, 等. 阿霉素对心肌细胞损伤的实验研究. 苏州大学学报: 医学版, 2008, 28(1): 47-49.
12.	Tokarska-Schlattner M, Wallimann T, Schlattner U. Alterations in myocardial energy metabolism induced by the anti-cancer drug doxorubicin. C R Biol, 2006, 329(9): 657-668.
13.	Mishra S, Murphy LC, Murphy TJ. The Prohibitins: emerging roles in diverse functions. J Cell Mol Med, 2006, 10(2): 353-363.
14.	Wood ZA, Schröder E, Robin HJ, et al. Structure, mechanism and regulation of peroxiredoxins. Trends Biochem Sci, 2003, 28(1): 32-40.
15.	Imura H, Caputo M, Lim K, et al. Pulmonary injury after cardiopulmonary bypass: beneficial effects of low-frequency mechanical ventilation. J Thorac Cardiovasc Surg, 2009, 137(6): 1530-1537.
16.	Barrier A, Olaya N, Chiappini F, et al. Ischemic preconditioning modulates the expression of several genes, leading to the overproduction of IL-1Ra, iNOS, and Bcl-2 in a human model of liver ischemia- reperfusion. FASEB J, 2005, 19(12): 1617-1626.

1. 朱飞, 宁金龙, 展望, 等. 缺血预处理对肌皮瓣缺血再灌注损伤的保护作用. 中华显微外科杂志, 1999, 22(4): 288-289.
2. Hellström PM. Vagotomy inhibits the effect of neurotensin on gastrointestinal transit in the rat. Acta Physiol Scand, 1986, 128(1): 47-55.
3. Murry CE, Jennings RB, Reimer RA. Preconditiony with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation, 1986, 74(5): 1124-1136.
4. 吴刚, 刘永锋, 杨蕾, 等. 阿霉素预处理替代缺血预处理提供鼠肝缺血耐受力的实验研究. 中华肝胆外科杂志, 2002, 8(5): 297-299.
5. Manson GF, Murphy GF, Anthenelli RM, et al. The role of oxygen-free radicals in ischemia tissue injury in island skin flaps. Ann Surg, 1983, 198(1): 87-90.
6. Dana A, Baxter GF, Yellon DM. Delayed or second window preconditioning induced by adenosine A1 receptor activation is inpendent of early generation of nitric oxide or late induction of inducible nitrix oxide synthase. J Cardiovasc Pharmacol, 2001, 38(2): 278-287.
7. 吴升华, 杨运昌, 王兆铭. 阿霉素心脏毒性中脂质过氧化的研究. 中国抗生素杂志, 1989, 14(5): 349-354.
8. 吴立春, 陈国桢, 方中良. 热休克蛋白与心肌缺血预适应延迟保护作用的关系. 医学综述, 2008, 8(15): 2252-2254.
9. 屈新才, 王继亮, 秦涛, 等. 供肝缺血预处理对大鼠肝移植缺血再灌注损伤的保护性作用. 中国普通外科杂志, 2007, 16(3): 240-244.
10. 汪晓筠, 谢智, 王建新, 等. 热休克联合缺血预处理对大鼠心肌缺血再灌注损伤早期的保护作用研究. 实用医学杂志, 2012, 28(5): 711-714.
11. 徐久宏, 张三典, 高耀明, 等. 阿霉素对心肌细胞损伤的实验研究. 苏州大学学报: 医学版, 2008, 28(1): 47-49.
12. Tokarska-Schlattner M, Wallimann T, Schlattner U. Alterations in myocardial energy metabolism induced by the anti-cancer drug doxorubicin. C R Biol, 2006, 329(9): 657-668.
13. Mishra S, Murphy LC, Murphy TJ. The Prohibitins: emerging roles in diverse functions. J Cell Mol Med, 2006, 10(2): 353-363.
14. Wood ZA, Schröder E, Robin HJ, et al. Structure, mechanism and regulation of peroxiredoxins. Trends Biochem Sci, 2003, 28(1): 32-40.
15. Imura H, Caputo M, Lim K, et al. Pulmonary injury after cardiopulmonary bypass: beneficial effects of low-frequency mechanical ventilation. J Thorac Cardiovasc Surg, 2009, 137(6): 1530-1537.
16. Barrier A, Olaya N, Chiappini F, et al. Ischemic preconditioning modulates the expression of several genes, leading to the overproduction of IL-1Ra, iNOS, and Bcl-2 in a human model of liver ischemia- reperfusion. FASEB J, 2005, 19(12): 1617-1626.

Chinese Journal of Reparative and Reconstructive Surgery

DOXORUBICIN PRECONDITIONING INSTEAD OF ISCHEMIC PRECONDITIONING IN PROVIDING ISCHEMIC TOLERANCE FOR RATS ABDOMEN ISLAND FLAPS

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