Comparative Study of Protective Effects of IPC, IPO, and IPC-IPO on Ischemic Reperfusion Injury of Pancreas Allograft of Rats_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Zhaohui ¹ , WANG Weizhong ² , LI Xi ¹ , NIU Wancheng ¹ , CHEN Dangying ¹ , ZHANG Yunmin. ¹

1.Department of General Surgery, The 97th Hospital of PLA, Xuzhou 221004, Jiangsu Province, China;;
2.Department of Gastrointestinal Surgery, Xijing Hospital of The Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China;

Corresponding author：

Keywords：

Pancreas transplantation; Ischemic reperfusion injury; Ischemic preconditioning; Ischemic postconditioning; Rat

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ObjectivesTo explore the mechanisms by which ischmic preconditioning (IPC), ischemic postconditioning (IPO) and IPCIPO exert influence on ischemic reperfusion injury (IRI) of the graft of SD rat after pancreas transplantation. MethodsAfter the establishment of diabetic SD rats model by using streptozotocin, 24 rats suffered from pancreas transplantation and were randomly averagely divided into four groups: I/R group, IPC group, IPO group, and IPC-IPO group. Six diabetic SD rats suffered with sham operation were served as SO group. The blood glucose level of rats in each group was detected before and after reperfusion, the contents of malonaldehyde (MDA) and super oxide dismutase (SOD) of pancreas allograft were tested at 2 h after reperfusion, and the apoptosis index (AI) of pancreas allograft was monitored by using TUNEL method. ResultsThe blood glucose level of rats in each group was not significantly different (P gt;0.05). In SO group, the blood glucose level of rats was significantly higher than other groups (P lt;0.01). The blood glucose levels of rats after reperfusion decreased from the levels before reperfusion in I/R group, IPC group, IPO group, and IPC-IPO group (P lt;0.05 or P lt;0.01), furthermore the blood glucose level of rats in I/R group was significantly higher than that in abovementioned three groups (P lt;0.01), although among which the difference was not markedly (P gt;0.05). When compared with I/R group, the MDA contents of rats after reperfusion in IPC group, IPO group， and IPC-IPO group decreased (P lt;0.01), while the SOD contents of rats after reperfusion increased (P lt;0.01). In rats of SO group, the MDA and SOD contents were significantly higher and lower than other groups, respectively (P lt;0.01). The MDA and SOD contents in IPC group, IPO group, and IPC-IPO group were not different (P gt;0.05). The AI of pancreas allograft at 2 h after reperfusion in I/R group 〔(47.31±4.52)%〕, IPC group 〔(26.25±3.17)%〕, IPO group 〔(24.73±3.62)%〕, and IPC-IPO group 〔(25.5±4.15)%〕 were higher than that in SO group 〔(3.16±0.53)%〕, P lt;0.01. The AI of pancreas allograft in IPC group, IPO group, and IPC-IPO group were not different (P gt;0.05), but they were lower than that in I/R group (P lt;0.01). Pathological results showed that injury of pancreas allograft in I/R group was most severe. ConclusionsIPO and IPC are associated with comparable effectiveness to protect graft from IRI during pancreas transplantation. The combined protective effects of IPC and IPO do not appear to be additive, which is equal to IPC or IPO alone.

Citation： ZHANG Zhaohui,WANG Weizhong,LI Xi,NIU Wancheng,CHEN Dangying,ZHANG Yunmin.. Comparative Study of Protective Effects of IPC, IPO, and IPC-IPO on Ischemic Reperfusion Injury of Pancreas Allograft of Rats. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(8): 844-848. doi: Copy

1.	Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium [J]. Circulation, 1986, 74(5): 11241136.
2.	蒋厚文, 陈闯, 郝立俊. 大鼠肢体缺血预处理对肝缺血/再灌注损伤的保护作用 [J]. 中国应用生理学杂志, 2010, 26(4): 502504.
3.	Sakamoto K, Nakahara T, Ishii K. RhoRho kinase pathway is involved in the protective effect of early ischemic preconditioning in the rat heart [J]. Biol Pharm Bull, 2011, 34(1): 156159.
4.	Kohr MJ, Sun J, Aponte A, et al. Simultaneous measurement of protein oxidation and Snitrosylation during preconditioning and ischemia/reperfusion injury with resinassisted capture [J]. Circ Res, 2011, 108(4): 418426.
5.	Zhao ZQ, Corvera JS, Halkos ME, et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning [J]. Am J Physiol Heart Circ Physiol, 2003, 285(2): H579H588.
6.	张召辉, 王为忠, 李玺, 等. 缺血预处理对大鼠移植胰腺缺血再灌注损伤的保护作用及其机制的研究 [J]. 中国现代普通外科进展, 2010, 13(8): 601604.
7.	张召辉, 王为忠, 李玺, 等. 不同缺血后处理方法对大鼠胰腺移植的保护作用及其机制 [J]. 中国组织工程研究与临床康复, 2010, 14(44): 82118214.
8.	Lee S, Tung KS, Koopmans H, et al. Pancreaticoduodenal transplantation in the rat [J]. Transplantation, 1972, 13(4): 421425.
9.	冷希圣, 黄萃庭. 大鼠同种异体全胰十二指肠移植治疗试验性糖尿病的初步观察 [J]. 中华实验外科杂志, 1986, 3(4): 165167.
10.	张召辉, 李玺. 大鼠胰十二指肠移植模型制作的手术技巧 [J]. 医学研究生学报, 2004, 17(9): 785787.
11.	Yun Y, Duan WG, Chen P, et al. Ischemic postconditioning modified renal oxidative stress and lipid peroxidation caused by ischemic reperfusion injury in rats [J]. Transplant Proc, 2009, 41(9): 35973602.
12.	de Rougemont O, Lehmann K, Clavien PA. Preconditioning, organ preservation, and postconditioning to prevent ischemiareperfusion injury to the liver [J]. Liver Transpl, 2009, 15(10): 11721182.
13.	Penna C, Tullio F, Moro F, et al. Effects of a protocol of ischemic postconditioning and/or captopril in hearts of normotensive and hypertensive rats [J]. Basic Res Cardiol, 2010, 105(2): 181192.
14.	Penna C, Perrelli MG, Raimondo S, et al. Postconditioning induces an antiapoptotic effect and preserves mitochondrial integrity in isolated rat hearts [J]. Biochim Biophys Acta, 2009, 1787(7): 794801.
15.	Wang N, Lu JG, He XL, et al. Effects of ischemic postconditioning on reperfusion injury in rat liver grafts after orthotopic liver transplantation [J]. Hepatol Res, 2009, 39(4): 382390.
16.	何桂珍, 董良广, 周开国, 等. 肠道缺血再灌注损伤时淋巴干结扎及谷氨酰胺营养干预的作用 [J]. 中国普外基础与临床杂志, 2010, 17(5): 443448.
17.	陈刚, 李学成, 吴国庆, 等. 携带IL13基因肝干细胞对冷缺血大鼠移植肝脏保护作用的研究 [J]. 中国普外基础与临床杂志, 2010, 17(2): 135141.
18.	秦勇, 党晓燕. 白藜芦醇对重症急性胰腺炎大鼠肠黏膜缺血再灌注损伤的保护作用 [J]. 中国普外基础与临床杂志, 2009, 16(10): 819823.
19.	邢军, 许评, 梁德森, 等. 异搏定对缺血再灌注大鼠胰腺细胞凋亡、组织钙及bcl2、cmyc表达的影响 [J]. 中国普外基础与临床杂志, 2006, 13(5): 545549.
20.	Kin H, Zhao ZQ, Sun HY, et al. Postconditioning attenuates myocardial ischemiareperfusion injury by inhibiting events in the early minutes of reperfusion [J]. Cardiovasc Res, 2004, 62(1): 7485.
21.	Vessey DA, Kelley M, Li L, et al. Sphingosine protects aging hearts from ischemia/reperfusion injury: Superiority to sphingosine 1phosphate and ischemic pre and postconditioning [J]. Oxid Med Cell Longev, 2009, 2(3): 146151.
22.	Dai AL, Fan LH, Zhang FJ, et al. Effects of sevoflurane preconditioning and postconditioning on rat myocardial stunning in ischemic reperfusion injury [J]. Zhejiang Univ Sci B, 2010, 11(4): 267274.
23.	Maslov LN. Role of erythropoietin in the ischemic preconditioning. Postconditioning and regeneration of brain after ischemia [J]. Ross Fiziol Zh Im I M Sechenova, 2010, 96(1): 2642.
24.	Prasad SS, Russell M, Nowakowska M. Neuroprotection induced in vitro by ischemic preconditioning and postconditioning: modulation of apoptosis and PI3KAkt pathways [J]. J Mol Neurosci, 2011, 43(3): 428442.
25.	Yang XM, Proctor JB, Cui L, et al. Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways [J]. Am Coll Cardiol, 2004, 44(5): 11031110.
26.	Halkos ME, Kerendi F, Corvera JS, et al. Myocardial protection with postconditioning is not enhanced by ischemic preconditioning [J]. Ann Thorac Surg, 2004, 78(3): 961969.

1. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium [J]. Circulation, 1986, 74(5): 11241136.
2. 蒋厚文, 陈闯, 郝立俊. 大鼠肢体缺血预处理对肝缺血/再灌注损伤的保护作用 [J]. 中国应用生理学杂志, 2010, 26(4): 502504.
3. Sakamoto K, Nakahara T, Ishii K. RhoRho kinase pathway is involved in the protective effect of early ischemic preconditioning in the rat heart [J]. Biol Pharm Bull, 2011, 34(1): 156159.
4. Kohr MJ, Sun J, Aponte A, et al. Simultaneous measurement of protein oxidation and Snitrosylation during preconditioning and ischemia/reperfusion injury with resinassisted capture [J]. Circ Res, 2011, 108(4): 418426.
5. Zhao ZQ, Corvera JS, Halkos ME, et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning [J]. Am J Physiol Heart Circ Physiol, 2003, 285(2): H579H588.
6. 张召辉, 王为忠, 李玺, 等. 缺血预处理对大鼠移植胰腺缺血再灌注损伤的保护作用及其机制的研究 [J]. 中国现代普通外科进展, 2010, 13(8): 601604.
7. 张召辉, 王为忠, 李玺, 等. 不同缺血后处理方法对大鼠胰腺移植的保护作用及其机制 [J]. 中国组织工程研究与临床康复, 2010, 14(44): 82118214.
8. Lee S, Tung KS, Koopmans H, et al. Pancreaticoduodenal transplantation in the rat [J]. Transplantation, 1972, 13(4): 421425.
9. 冷希圣, 黄萃庭. 大鼠同种异体全胰十二指肠移植治疗试验性糖尿病的初步观察 [J]. 中华实验外科杂志, 1986, 3(4): 165167.
10. 张召辉, 李玺. 大鼠胰十二指肠移植模型制作的手术技巧 [J]. 医学研究生学报, 2004, 17(9): 785787.
11. Yun Y, Duan WG, Chen P, et al. Ischemic postconditioning modified renal oxidative stress and lipid peroxidation caused by ischemic reperfusion injury in rats [J]. Transplant Proc, 2009, 41(9): 35973602.
12. de Rougemont O, Lehmann K, Clavien PA. Preconditioning, organ preservation, and postconditioning to prevent ischemiareperfusion injury to the liver [J]. Liver Transpl, 2009, 15(10): 11721182.
13. Penna C, Tullio F, Moro F, et al. Effects of a protocol of ischemic postconditioning and/or captopril in hearts of normotensive and hypertensive rats [J]. Basic Res Cardiol, 2010, 105(2): 181192.
14. Penna C, Perrelli MG, Raimondo S, et al. Postconditioning induces an antiapoptotic effect and preserves mitochondrial integrity in isolated rat hearts [J]. Biochim Biophys Acta, 2009, 1787(7): 794801.
15. Wang N, Lu JG, He XL, et al. Effects of ischemic postconditioning on reperfusion injury in rat liver grafts after orthotopic liver transplantation [J]. Hepatol Res, 2009, 39(4): 382390.
16. 何桂珍, 董良广, 周开国, 等. 肠道缺血再灌注损伤时淋巴干结扎及谷氨酰胺营养干预的作用 [J]. 中国普外基础与临床杂志, 2010, 17(5): 443448.
17. 陈刚, 李学成, 吴国庆, 等. 携带IL13基因肝干细胞对冷缺血大鼠移植肝脏保护作用的研究 [J]. 中国普外基础与临床杂志, 2010, 17(2): 135141.
18. 秦勇, 党晓燕. 白藜芦醇对重症急性胰腺炎大鼠肠黏膜缺血再灌注损伤的保护作用 [J]. 中国普外基础与临床杂志, 2009, 16(10): 819823.
19. 邢军, 许评, 梁德森, 等. 异搏定对缺血再灌注大鼠胰腺细胞凋亡、组织钙及bcl2、cmyc表达的影响 [J]. 中国普外基础与临床杂志, 2006, 13(5): 545549.
20. Kin H, Zhao ZQ, Sun HY, et al. Postconditioning attenuates myocardial ischemiareperfusion injury by inhibiting events in the early minutes of reperfusion [J]. Cardiovasc Res, 2004, 62(1): 7485.
21. Vessey DA, Kelley M, Li L, et al. Sphingosine protects aging hearts from ischemia/reperfusion injury: Superiority to sphingosine 1phosphate and ischemic pre and postconditioning [J]. Oxid Med Cell Longev, 2009, 2(3): 146151.
22. Dai AL, Fan LH, Zhang FJ, et al. Effects of sevoflurane preconditioning and postconditioning on rat myocardial stunning in ischemic reperfusion injury [J]. Zhejiang Univ Sci B, 2010, 11(4): 267274.
23. Maslov LN. Role of erythropoietin in the ischemic preconditioning. Postconditioning and regeneration of brain after ischemia [J]. Ross Fiziol Zh Im I M Sechenova, 2010, 96(1): 2642.
24. Prasad SS, Russell M, Nowakowska M. Neuroprotection induced in vitro by ischemic preconditioning and postconditioning: modulation of apoptosis and PI3KAkt pathways [J]. J Mol Neurosci, 2011, 43(3): 428442.
25. Yang XM, Proctor JB, Cui L, et al. Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways [J]. Am Coll Cardiol, 2004, 44(5): 11031110.
26. Halkos ME, Kerendi F, Corvera JS, et al. Myocardial protection with postconditioning is not enhanced by ischemic preconditioning [J]. Ann Thorac Surg, 2004, 78(3): 961969.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Comparative Study of Protective Effects of IPC, IPO, and IPC-IPO on Ischemic Reperfusion Injury of Pancreas Allograft of Rats

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