目的 研究大鼠肝臟熱缺血后經(jīng)門靜脈和肝動(dòng)脈不同時(shí)序灌注對(duì)其損傷的影響,探索是否可由此減輕大鼠肝臟缺血再灌注損傷及其可能的機(jī)理。
方法 選用健康雄性SD大鼠96只,按隨機(jī)數(shù)字表法等分成6組,1組為假手術(shù)組,其余5組為實(shí)驗(yàn)組。假手術(shù)組(16只)只作開腹和肝門部解剖; 實(shí)驗(yàn)組(共5組,每組16只)根據(jù)再灌注時(shí)門靜脈和肝動(dòng)脈不同開放時(shí)序分組: 先開放門靜脈1 min后再開放肝動(dòng)脈組、先開放門靜脈2 min后再開放肝動(dòng)脈組、先開放肝動(dòng)脈1 min后再開放門靜脈組、先開放肝動(dòng)脈2 min后再開放門靜脈組及同時(shí)開放門靜脈和肝動(dòng)脈組。各組分別于術(shù)后2 h和4 h檢測血清中ALT和AST值,肝組織中丙二醛(MDA)、超氧化物歧化酶(SOD)及谷胱甘肽(GSH)含量變化; 采用病理組織切片HE染色觀察肝組織損傷情況; TUNEL法檢測各組肝組織細(xì)胞凋亡情況。
結(jié)果 假手術(shù)組大鼠肝臟基本正常,各指標(biāo)均好于各實(shí)驗(yàn)組,差異均有統(tǒng)計(jì)學(xué)意義(P<0.01)。在各實(shí)驗(yàn)組中先開放門靜脈1 min后再開放肝動(dòng)脈組大鼠肝臟缺血再灌注損傷最輕,其ALT、AST、MDA和凋亡指數(shù)值均明顯低于其他各實(shí)驗(yàn)組,差異有統(tǒng)計(jì)學(xué)意義(P<0.05或P<0.01),并且其SOD和GSH值均高于其他各實(shí)驗(yàn)組,差異亦有統(tǒng)計(jì)學(xué)意義(P<0.05或P<0.01)。肝組織HE染色也顯示,先開放門靜脈1 min后再開放肝動(dòng)脈組大鼠肝組織損傷較其他各實(shí)驗(yàn)組輕。
結(jié)論 肝臟熱缺血后,通過短暫開放門靜脈再開放肝動(dòng)脈的措施可以減輕大鼠肝臟缺血再灌注損傷,可能與降低活性氧的產(chǎn)生及保護(hù)肝臟抗氧化系統(tǒng)有關(guān)。
引用本文: 顧國文,李相成,孫勇. 肝門阻斷時(shí)肝動(dòng)脈與門靜脈不同開放時(shí)序?qū)Ω闻K缺血再灌注的影響. 中國普外基礎(chǔ)與臨床雜志, 2009, 16(3): 203-207. doi: 復(fù)制
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2. | 胡軍, 劉志蘇, 孫權(quán), 等. 缺血后處理對(duì)肝臟缺血再灌注中肝竇內(nèi)皮細(xì)胞損傷的保護(hù)作用 [J]. 肝臟, 2004; 9(1):21. |
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4. | Sun K, Liu ZS, Sun Q. Role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning [J]. World J Gastroenterol, 2004; 10(13):1934. |
5. | Puhl G, Schaser KD, Pust D, et al. The delay of rearterialization after initial portal reperfusion in living donor liver transplantation significantly determines the development of microvascular graft dysfunction [J]. J Hepatol, 2004; 41(2):299. |
6. | van As AB, Lotz Z, Tyler M, et al. Reperfusion injury associated with portal venous and hepatic arterial perfusion in liver transplantation [J].Transplantation, 2002; 74(2):158. |
7. | Moreno C, Sabaté A, Figueras J, et al. Hemodynamic profile and tissular oxygenation in orthotopic liver transplantation: Influence of hepatic artery or portal vein revascularization of the graft [J]. Liver Transpl, 2006; 12(11):1607. |
8. | Polak WG, Porte RJ. The sequence of revascularization in liver transplantation: it does make a difference [J]. Liver Transpl, 2006; 12(11):1566. |
9. | Vinten-Johansen J, Zhao ZQ, Zatta AJ, et al. Postconditioning—A new link in nature’s armor against myocardial ischemia-reperfusion injury [J]. Basic Res Cardiol, 2005; 100(4):295. |
10. | Glantzounis GK, Salacinski HJ, Yang W, et al. The contemporary role of antioxidant therapy in attenuating liver ischemia-reperfusion injury: a review [J]. Liver Transpl, 2005; 11(9):1031. |
11. | Zhang W, Wang M, Xie HY, et al. Role of reactive oxygen species in mediating hepatic ischemia-reperfusion injury and its therapeutic applications in liver transplantation [J]. Transplant Proc, 2007; 39(5):1332. |
12. | Becker LB. New concepts in reactive oxygen species and cardiovascular reperfusion physiology [J]. Cardiovasc Res, 2004; 61(3):461. |
13. | Wu BQ, Chu WW, Zhang LY, et al. Protection of preconditioning, postconditioning and combined therapy against hepatic ischemia/reperfusion injury [J]. Chin J Traumatol, 2007; 10(4):223. |
14. | 冉江華, 郭永章, 李立, 等. 重組人生長激素對(duì)大鼠肝臟缺血再灌注損傷的保護(hù)作用 [J]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(5):555. |
15. | 王科, 王學(xué)浩, 張峰, 等. 誘導(dǎo)HO-1改善氧化應(yīng)激狀態(tài)減輕老年供肝缺血-再灌注損傷 [J]. 中國普外基礎(chǔ)與臨床雜志, 2005; 12(2):109. |
16. | Demirbilek S, Karaman A, Gürünlüoglu K, et al. Polyenylphosphatidylcholine pretreatment protects rat liver from ischemia/reperfusion injury [J]. Hepatol Res, 2006; 34(2):84. |
17. | Yuan GJ, Ma JC, Gong ZJ, et al. Modulation of liver oxidant-antioxidant system by ischemic preconditioning during ischemia/reperfusion injury in rats [J]. World J Gastroenterol, 2005; 11(12):1825. |
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20. | Piper HM, Abdallah Y, Schfer C. The first minutes of reperfusion: a window of opportunity for cardioprotection [J]. Cardiovasc Res, 2004; 61(3):365. |
21. | Kloner RA, Rezkalla SH. Preconditioning, postconditioning and their application to clinical cardiology [J]. Cardiovasc Res, 2006; 70(2):297. |
22. | Yellon DM, Hausenloy DJ. Realizing the clinical potential of ischemic preconditioning and postconditioning [J]. Nat Clin Pract Cardiovasc Med, 2005; 2(11):568. |
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- 1. Romanque UP, Uribe MM, Videla LA. Molecular mechanisms in liver ischemic-reperfusion injury and ischemic preconditioning [J]. Rev Med Chil, 2005; 133(4):469.
- 2. 胡軍, 劉志蘇, 孫權(quán), 等. 缺血后處理對(duì)肝臟缺血再灌注中肝竇內(nèi)皮細(xì)胞損傷的保護(hù)作用 [J]. 肝臟, 2004; 9(1):21.
- 3. Galaris D, Barbouti A, Korantzopoulos P. Oxidative stress in hepatic ischemia-reperfusion injury: the role of antioxidants and iron chelating compounds [J]. Curr Pharm Des, 2006; 12(23):2875.
- 4. Sun K, Liu ZS, Sun Q. Role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning [J]. World J Gastroenterol, 2004; 10(13):1934.
- 5. Puhl G, Schaser KD, Pust D, et al. The delay of rearterialization after initial portal reperfusion in living donor liver transplantation significantly determines the development of microvascular graft dysfunction [J]. J Hepatol, 2004; 41(2):299.
- 6. van As AB, Lotz Z, Tyler M, et al. Reperfusion injury associated with portal venous and hepatic arterial perfusion in liver transplantation [J].Transplantation, 2002; 74(2):158.
- 7. Moreno C, Sabaté A, Figueras J, et al. Hemodynamic profile and tissular oxygenation in orthotopic liver transplantation: Influence of hepatic artery or portal vein revascularization of the graft [J]. Liver Transpl, 2006; 12(11):1607.
- 8. Polak WG, Porte RJ. The sequence of revascularization in liver transplantation: it does make a difference [J]. Liver Transpl, 2006; 12(11):1566.
- 9. Vinten-Johansen J, Zhao ZQ, Zatta AJ, et al. Postconditioning—A new link in nature’s armor against myocardial ischemia-reperfusion injury [J]. Basic Res Cardiol, 2005; 100(4):295.
- 10. Glantzounis GK, Salacinski HJ, Yang W, et al. The contemporary role of antioxidant therapy in attenuating liver ischemia-reperfusion injury: a review [J]. Liver Transpl, 2005; 11(9):1031.
- 11. Zhang W, Wang M, Xie HY, et al. Role of reactive oxygen species in mediating hepatic ischemia-reperfusion injury and its therapeutic applications in liver transplantation [J]. Transplant Proc, 2007; 39(5):1332.
- 12. Becker LB. New concepts in reactive oxygen species and cardiovascular reperfusion physiology [J]. Cardiovasc Res, 2004; 61(3):461.
- 13. Wu BQ, Chu WW, Zhang LY, et al. Protection of preconditioning, postconditioning and combined therapy against hepatic ischemia/reperfusion injury [J]. Chin J Traumatol, 2007; 10(4):223.
- 14. 冉江華, 郭永章, 李立, 等. 重組人生長激素對(duì)大鼠肝臟缺血再灌注損傷的保護(hù)作用 [J]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(5):555.
- 15. 王科, 王學(xué)浩, 張峰, 等. 誘導(dǎo)HO-1改善氧化應(yīng)激狀態(tài)減輕老年供肝缺血-再灌注損傷 [J]. 中國普外基礎(chǔ)與臨床雜志, 2005; 12(2):109.
- 16. Demirbilek S, Karaman A, Gürünlüoglu K, et al. Polyenylphosphatidylcholine pretreatment protects rat liver from ischemia/reperfusion injury [J]. Hepatol Res, 2006; 34(2):84.
- 17. Yuan GJ, Ma JC, Gong ZJ, et al. Modulation of liver oxidant-antioxidant system by ischemic preconditioning during ischemia/reperfusion injury in rats [J]. World J Gastroenterol, 2005; 11(12):1825.
- 18. Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: united at reperfusion [J]. Pharmacol Ther, 2007; 116(2):173.
- 19. Davidson SM, Hausenloy D, Duchen MR, et al. Signalling via the reperfusion injury signalling kinase (RISK) pathway links closure of the mitochondrial permeability transition pore to cardioprotection [J]. Int J Biochem Cell Biol, 2006; 38(3):414.
- 20. Piper HM, Abdallah Y, Schfer C. The first minutes of reperfusion: a window of opportunity for cardioprotection [J]. Cardiovasc Res, 2004; 61(3):365.
- 21. Kloner RA, Rezkalla SH. Preconditioning, postconditioning and their application to clinical cardiology [J]. Cardiovasc Res, 2006; 70(2):297.
- 22. Yellon DM, Hausenloy DJ. Realizing the clinical potential of ischemic preconditioning and postconditioning [J]. Nat Clin Pract Cardiovasc Med, 2005; 2(11):568.
- 23. Rastaldo R, Penna C, Cappello S, et al.Ischemic postconditioning: an effective strategy of myocardial protection? [J]. G Ital Cardiol (Rome), 2006; 7(7):464.