目的 探討改變血紅素氧化酶-1(HO-1)的活性對大鼠同種異體原位肝移植的影響。
方法 用二袖套法建立大鼠同種異體原位肝移植模型,實(shí)驗(yàn)分為4組: 實(shí)驗(yàn)對照組(n=44): 供體鼠術(shù)前24 h腹腔注射生理鹽水5 ml/kg; 氯化血紅素組(n=44): 供體鼠術(shù)前24 h腹腔注射氯化血紅素100 mg/kg,在供肝4 ℃生理鹽水保存期間,經(jīng)門靜脈注入氯化血紅素100 mg/kg; 鋅原卟啉組(n=44): 供體鼠術(shù)前24 h腹腔注射鋅原卟啉5 mg/kg,在供肝4 ℃生理鹽水保存期間,經(jīng)門靜脈注入鋅原卟啉5 mg/kg; 正常大鼠作為正常對照組(n=5)。分別應(yīng)用RT-PCR及免疫組化技術(shù)檢測移植肝臟中HO-1 mRNA及蛋白表達(dá),并用流式細(xì)胞儀分析移植肝臟肝細(xì)胞的凋亡率。
結(jié)果 肝移植術(shù)后供體肝HO-1表達(dá)增強(qiáng)。肝移植術(shù)后氯化血紅素組HO-1 mRNA表達(dá)水平高于實(shí)驗(yàn)對照組,血清ALT和AST水平低于實(shí)驗(yàn)對照組(P<0.05); 鋅原卟啉組術(shù)后肝組織HO-1 mRNA表達(dá)水平低于實(shí)驗(yàn)對照組(P<0.05),血清ALT和AST水平高于實(shí)驗(yàn)對照組(P<0.05)。肝移植術(shù)后48 h肝細(xì)胞凋亡率鋅原卟啉組最高,氯化血紅素組最低,實(shí)驗(yàn)對照組介于二者之間,組間差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。術(shù)后7 d實(shí)驗(yàn)對照組、氯化血紅素組及鋅原卟啉組3組的生存大鼠分別為7/12、9/12和4/12,組間差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。
結(jié)論 肝移植手術(shù)過程可促進(jìn)大鼠肝臟HO-1表達(dá)增強(qiáng); 術(shù)前采用藥物誘導(dǎo)HO-1可降低移植術(shù)后肝細(xì)胞凋亡率,減輕肝臟損傷程度,提高術(shù)后生存率。
引用本文: 張黎,程力,李更生,崔彬,張緊. 血紅素氧化酶-1在大鼠肝移植中保護(hù)作用的研究. 中國普外基礎(chǔ)與臨床雜志, 2008, 15(9): 665-670. doi: 復(fù)制
版權(quán)信息: ?四川大學(xué)華西醫(yī)院華西期刊社《中國普外基礎(chǔ)與臨床雜志》版權(quán)所有,未經(jīng)授權(quán)不得轉(zhuǎn)載、改編
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2. | 陳孝平主編. 外科常用實(shí)驗(yàn)方法及動(dòng)物模型的建立 [M]. 第1版. 北京: 人民衛(wèi)生出版社, 2003∶451~452. |
3. | Lu F, Zander DS, Visner GA. Increased expression of heme oxygenase-1 in human lung transplantation [J]. J Heart Lung Transplant, 2002; 21(10)∶1120. |
4. | Kobayashi T, Sato Y, Yamamoto S, et al. Augmentation of heme oxygenase-1 expression in the graft immediately after implantation in adult living-donor liver transplantation [J]. Transplantation, 2005; 79(8)∶977. |
5. | Yang ZF, Tsui TY, Ho DW, et al. Heme oxygenase-1 potentiates the survival of small-for-size liver graft [J]. Liver Transpl, 2004; 10(6)∶784. |
6. | Otterbein LE, Zukerbraun BS, Haga M, et al. Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury [J]. Nat Med, 2003; 9(2)∶183. |
7. | Katori M, Busuttil RW, Kupiec-Weglinski JW. Heme oxygenase-1 system in organ transplantation [J]. Transplantation, 2002; 74(7)∶905. |
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9. | 馬躍峰, 李相成, 姚愛華, 等. 缺血預(yù)處理對大鼠肝臟移植物再灌注早期NF-κB活性的影響及意義 [J]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(5)∶531. |
10. | Coito AJ, Buelow R, Shen XD, et al. Heme oxygenase-1 gene transfer inhibits inducible nitric oxide synthase expression and protects genetically fat Zucker rat livers from ischemia-reperfusion injury [J].Transplantation, 2002; 74(1)∶96. |
11. | 丁紀(jì)明, 陳平, 張林, 等. 切應(yīng)力對大鼠肝竇內(nèi)皮細(xì)胞分泌功能的影響 [J]. 中國普外基礎(chǔ)與臨床雜志, 2005; 12(5)∶455. |
12. | 張黎, 黃加棟, 楊鎮(zhèn), 等. 門靜脈高壓大鼠血紅素氧化酶-1 mRNA的表達(dá) [J]. 中國普通外科雜志, 2002; 11(9)∶551. |
13. | 張黎, 蔣進(jìn)皎, 楊鎮(zhèn), 等. 肝硬變門靜脈高壓癥患者血紅素氧化酶-1的表達(dá) [J]. 中國普通外科雜志, 2003; 12(6)∶419. |
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15. | 杜敦峰, 昌盛, 陳必成, 等. 血紅素氧合酶-1抑制T淋巴細(xì)胞對血管內(nèi)皮細(xì)胞的粘附作用 [J]. 中華器官移植雜志, 2005; 26(6)∶363. |
16. | 張中明, 陳德海, 董紅燕, 等. 血紅素氧化酶-1對紫紺型兔心臟復(fù)氧及缺血再灌注損傷的保護(hù)作用 [J]. 中華實(shí)驗(yàn)外科雜志,2005; 22(4)∶510. |
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18. | Kato H, Amersi F, Buelow R, et al. Heme oxygenase-1 overexpression protects rat livers from ischemia/reperfusion injury with extended cold preservation [J]. Am J Transplant, 2001; 1(2)∶121. |
19. | 孟凡強(qiáng), 姜洪池, 孫學(xué)英, 等. 苦參素對大鼠肝缺血再灌注中肝細(xì)胞的保護(hù)作用及其機(jī)制探討 [J]. 中華醫(yī)學(xué)雜志, 2005; 85(28)∶1991. |
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21. | Sato K, Balla J, Otterbein L, et al. Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants [J]. J Immunol, 2001; 166(6)∶4185. |
- 1. Kamada N, Calne RY. A surgical experience with five hundred thirty liver transplants in the rat [J]. Surgery, 1983; 93 (1 Pt 1)∶64.
- 2. 陳孝平主編. 外科常用實(shí)驗(yàn)方法及動(dòng)物模型的建立 [M]. 第1版. 北京: 人民衛(wèi)生出版社, 2003∶451~452.
- 3. Lu F, Zander DS, Visner GA. Increased expression of heme oxygenase-1 in human lung transplantation [J]. J Heart Lung Transplant, 2002; 21(10)∶1120.
- 4. Kobayashi T, Sato Y, Yamamoto S, et al. Augmentation of heme oxygenase-1 expression in the graft immediately after implantation in adult living-donor liver transplantation [J]. Transplantation, 2005; 79(8)∶977.
- 5. Yang ZF, Tsui TY, Ho DW, et al. Heme oxygenase-1 potentiates the survival of small-for-size liver graft [J]. Liver Transpl, 2004; 10(6)∶784.
- 6. Otterbein LE, Zukerbraun BS, Haga M, et al. Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury [J]. Nat Med, 2003; 9(2)∶183.
- 7. Katori M, Busuttil RW, Kupiec-Weglinski JW. Heme oxygenase-1 system in organ transplantation [J]. Transplantation, 2002; 74(7)∶905.
- 8. 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.
- 9. 馬躍峰, 李相成, 姚愛華, 等. 缺血預(yù)處理對大鼠肝臟移植物再灌注早期NF-κB活性的影響及意義 [J]. 中國普外基礎(chǔ)與臨床雜志, 2006; 13(5)∶531.
- 10. Coito AJ, Buelow R, Shen XD, et al. Heme oxygenase-1 gene transfer inhibits inducible nitric oxide synthase expression and protects genetically fat Zucker rat livers from ischemia-reperfusion injury [J].Transplantation, 2002; 74(1)∶96.
- 11. 丁紀(jì)明, 陳平, 張林, 等. 切應(yīng)力對大鼠肝竇內(nèi)皮細(xì)胞分泌功能的影響 [J]. 中國普外基礎(chǔ)與臨床雜志, 2005; 12(5)∶455.
- 12. 張黎, 黃加棟, 楊鎮(zhèn), 等. 門靜脈高壓大鼠血紅素氧化酶-1 mRNA的表達(dá) [J]. 中國普通外科雜志, 2002; 11(9)∶551.
- 13. 張黎, 蔣進(jìn)皎, 楊鎮(zhèn), 等. 肝硬變門靜脈高壓癥患者血紅素氧化酶-1的表達(dá) [J]. 中國普通外科雜志, 2003; 12(6)∶419.
- 14. Rentsch M, Kienle K, Mueller T, et al. Adenoviral bcl-2 transfer improves survival and early graft function after ischemia and reperfusion in rat liver transplantation [J]. Transplantation, 2005; 80(10)∶1461.
- 15. 杜敦峰, 昌盛, 陳必成, 等. 血紅素氧合酶-1抑制T淋巴細(xì)胞對血管內(nèi)皮細(xì)胞的粘附作用 [J]. 中華器官移植雜志, 2005; 26(6)∶363.
- 16. 張中明, 陳德海, 董紅燕, 等. 血紅素氧化酶-1對紫紺型兔心臟復(fù)氧及缺血再灌注損傷的保護(hù)作用 [J]. 中華實(shí)驗(yàn)外科雜志,2005; 22(4)∶510.
- 17. 邵堂雷, 蔡偉耀, 楊偉平, 等. 供肝冷熱缺血移植后損傷與炎癥細(xì)胞的關(guān)系 [J]. 中華肝臟病雜志, 2002; 10(6)∶455.
- 18. Kato H, Amersi F, Buelow R, et al. Heme oxygenase-1 overexpression protects rat livers from ischemia/reperfusion injury with extended cold preservation [J]. Am J Transplant, 2001; 1(2)∶121.
- 19. 孟凡強(qiáng), 姜洪池, 孫學(xué)英, 等. 苦參素對大鼠肝缺血再灌注中肝細(xì)胞的保護(hù)作用及其機(jī)制探討 [J]. 中華醫(yī)學(xué)雜志, 2005; 85(28)∶1991.
- 20. Katori M, Buelow R, Ke B, et al. Heme oxygenase-1 overexpression protects rat hearts from cold ischemia/reperfusion injury via an antiapoptotic pathway [J]. Transplantation, 2002; 73(2)∶287.
- 21. Sato K, Balla J, Otterbein L, et al. Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants [J]. J Immunol, 2001; 166(6)∶4185.