結扎腹主動脈加雙側腹壁陰部動脈在大鼠后肢缺血模型中的應用_《中國普外基礎與臨床雜志》

作者：

劉坤 ¹ , 楊琨 ² , 羅軍 ¹ , 王洋 ¹ , 李新喜 ¹ , 白超 ¹ , 揭月高 ¹

1.新疆醫科大學第一附屬醫院消化血管外科中心(烏魯木齊 830054);;
2.新疆醫科大學第一附屬醫院燒傷整形科(烏魯木齊 830054);

關鍵詞：

肢體缺血腹主動脈腹壁陰部動脈結扎動物模型

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目的探討結扎腹主動脈加雙側腹壁陰部動脈在SD大鼠后肢動脈缺血模型中的應用價值。
方法將38只大鼠按隨機數字表法隨機分為假手術組(n=12)、結扎腹主動脈組(n=12)和結扎腹主動脈加雙側腹壁陰部動脈組(n=14)。氯胺酮6 mg/100 g腹腔注射麻醉大鼠，開腹后按各組不同的處理方法處理血管，觀察術后2周和4周時各組后肢肌力、蒼白等情況，同時取股靜脈血做血氣分析，并取后肢骨骼肌行HE染色。
結果結扎腹主動脈加雙側腹壁陰部動脈組術后3 d內死亡2只大鼠，其余大鼠均存活。假手術組術后無明顯異常。結扎腹主動脈組術后立即出現后肢蒼白、活動差; 2周時后肢蒼白、皮溫低有好轉; 4周時恢復正常。結扎腹主動脈加雙側腹壁陰部動脈組術后2周時后肢缺血明顯，肢體蒼白、運動差; 4周時仍有較明顯的肌力異常、蒼白等表現。各組均無后肢壞死。結扎腹主動脈加雙側腹壁陰部動脈組在術后2和4周時的肌力和蒼白情況均較假手術組差(P lt;0.05); 與結扎腹主動脈組比較,在術后4周時肢體蒼白情況仍較差(P lt;0.05)。各組內不同時相間比較,差異均無統計學意義(P gt;0.05)。結扎腹主動脈加雙側腹壁陰部動脈組的靜脈血氧分壓在術后2及4周時明顯低于其他2組(P lt;0.05)。HE染色：對照組顯示正常的橫紋肌結構；結扎腹主動脈組術后2周可見細胞染色不均，腫脹，橫紋消失，部分細胞核染色深，4周時恢復正常；結扎腹主動脈加雙側腹壁陰部動脈組術后2周及4周見骨骼肌染色不均，細胞腫脹明顯，橫紋消失，部分細胞核染色深，密集，細胞間隙加大，但未見明顯的細胞壞死。
結論結扎腹主動脈加雙側腹壁陰部動脈可制作穩定的SD大鼠后肢缺血模型。

引用本文： 劉坤,楊琨,羅軍,王洋,李新喜,白超,揭月高. 結扎腹主動脈加雙側腹壁陰部動脈在大鼠后肢缺血模型中的應用. 中國普外基礎與臨床雜志, 2010, 17(3): 258-262. doi: 復制

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3.	Sumi M, Sata M, Toya N, et al. Transplantation of adipose stromal cells, but not mature adipocytes, augments ischemiainduced angiogenesis [J]. Life Sci, 2007; 80(6): 559565.
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5.	Ikenaga S, Hamano K, Nishida M, et al. Autologous bone marrow implantation induced angiogenesis and improved deteriorated exercise capacity in a rat ischemic hindlimb model [J]. J Surg Res, 2001; 96(2): 277283.
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7.	Iba O, Matsubara H, Nozawa Y, et al. Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs [J]. Circulation, 2002; 106(15): 20192025.
8.	Iwaguro H, Yamaguchi J, Kalka C, et al. Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration [J]. Circulation, 2002; 105(6): 732738.
9.	Padilla L, Krtzsch E, Schalch P, et al. Administration of bone marrow cells into surgically induced fibrocollagenous tunnels induces angiogenesis in ischemic rat hindlimb model [J]. Microsurgery, 2003; 23(6): 568574.
10.	劉文亮, 尹邦良, 喻風雷, 等. 骨髓單個核細胞缺血組織局部移植對血運重建的影響 [J]. 中南大學學報(醫學版), 2004; 29(5): 572576.
11.	Hiasa K, Ishibashi M, Ohtani K, et al. Gene transfer of stromal cellderived factor1α enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthaserelated pathway: nextgeneration chemokine therapy for therapeutic neovascularization [J]. Circulation, 2004; 109(20): 24542461.
12.	Sato Y, Matsui K, Ajiki T, et al. Can a bone marrow cell contribute to organ regeneration? In vivo analysis using transgenic rats with reporter genes [J]. Transplant Proc, 2005; 37(1): 273275.
13.	Otsuka H, Akashi H, Murohara T, et al. The prostacyclin analog beraprost sodium augments the efficacy of therapeutic angiogenesis induced by autologous bone marrow cells [J]. Ann Vasc Surg, 2006; 20(5): 646652.
14.	de Nigris F, Balestrieri ML, WilliamsIgnarro S, et al. Therapeutic effects of autologous bone marrow cells and metabolic intervention in the ischemic hindlimb of spontaneously hypertensive rats involve reduced cell senescence and CXCR4/Akt/eNOS pathways [J]. J Cardiovasc Pharmacol, 2007; 50(4): 424433.
15.	Qin SL, Li TS, Kubo M, et al. Transient increase of cytokines in the acute ischemic tissue is beneficial to cellbased therapeutic angiogenesis [J]. Circ J, 2008; 72(12): 20752080.
16.	Wragg A, Mellad JA, Beltran LE, et al. VEGFR1/CXCR4positive progenitor cells modulate local inflammation and augment tissue perfusion by a SDF1dependent mechanism [J]. J Mol Med, 2008; 86(11): 12211232.
17.	Iohara K, Zheng L, Wake H, et al. A novel stem cell source for vasculogenesis in ischemia: subfraction of side population cells from dental pulp [J]. Stem Cells, 2008; 26(9): 24082418.
18.	Tajima H, IwaiTakano M, Yaoita H, et al. Mast cells contribute to flow restoration by bone marrow cell transplantation in rats with ischemic limbs [J]. Int Heart J, 2009; 50(2): 247257.
19.	汪忠鎬, 李震. 我國血管外科的現狀和發展 [J]. 中國普外基礎與臨床雜志, 2006; 13(6): 625628.
20.	梁翠宏. Wistar大鼠后肢缺血模型的實驗研究 [D]. 山東大學, 2005: 17.
21.	劉萬里, 薛茜, 曹明芹，等. 用 SPSS實現完全隨機設計多組比較秩和檢驗的多重比較 [J]. 地方病通報, 2007; 22(2): 2729.
22.	崔世軍，俞恒錫，滕旭，等. 家兔后肢缺血模型的制作 [J]. 中國比較醫學雜志, 2003; 13(1): 3638.
23.	Heil M, Ziegelhoeffer T, Pipp F, et al. Blood monocyte concentration is critical for enhancement of collateral artery growth [J]. Am J Physiol Heart Circ Physiol, 2002; 283(6): H2411H2419.
24.	霍鑫，馮金煒，劉方峰，等. pEGFPC1/Akt體外轉染骨髓間充質干細胞對后肢缺血大鼠血管生成的影響 [J]. 中國普外基礎與臨床雜志, 2008; 15(6): 402407.
25.	Iwatsuki Y, Sakata C, Kawasaki T, et al. Experimental model of lower limb ischemia in rats and the effect of YM466, an oral direct factor Xa inhibitor [J]. Biol Pharm Bull, 2007; 30(10): 18741877.
26.	梁翠宏，田鏵，徐蘊，等. 結扎切斷法與白芨微粒栓塞法建立大鼠后肢缺血模型效果比較 [J]. 山東大學學報(醫學版), 2007; 45(10): 10081010.
27.	Pu LQ, Jackson S, Lachapelle KJ, et al. A persistent hindlimb ischemia model in the rabbit [J]. J Invest Surg, 1994; 7(1): 4960.
28.	梁翠宏，田鏵，徐蘊，等. 結扎切斷法制作大鼠后肢缺血模型的效果 [J]. 解剖學雜志, 2006; 29(6): 795797.
29.	楊安峰, 王平. 大鼠的解剖和組織 [M]. 北京: 科學出版社, 1980: 124130.

1. Isner JM, Walsh K, Symes J, et al. Arterial gene transfer for therapeutic angiogenesis in patients with peripheral artery disease [J]. Hum Gene Ther, 1996; 7(8): 959988.
2. Tatsumi T, Matsubara H. Therapeutic angiogenesis for peripheral arterial disease and ischemic heart disease by autologous bone marrow cells implantation [J]. Nippon Rinsho, 2006; 64(11): 21262134.
3. Sumi M, Sata M, Toya N, et al. Transplantation of adipose stromal cells, but not mature adipocytes, augments ischemiainduced angiogenesis [J]. Life Sci, 2007; 80(6): 559565.
4. Hamano K, Li TS, Kobayashi T, et al. The induction of angiogenesis by the implantation of autologous bone marrow cells: a novel and simple therapeutic method [J]. Surgery, 2001; 130(1): 4454.
5. Ikenaga S, Hamano K, Nishida M, et al. Autologous bone marrow implantation induced angiogenesis and improved deteriorated exercise capacity in a rat ischemic hindlimb model [J]. J Surg Res, 2001; 96(2): 277283.
6. Kawamoto A, Asahara T, Losordo DW. Transplantation of endothelial progenitor cells for therapeutic neovascularization [J]. Cardiovasc Radiat Med, 2002; 3(34): 221225.
7. Iba O, Matsubara H, Nozawa Y, et al. Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs [J]. Circulation, 2002; 106(15): 20192025.
8. Iwaguro H, Yamaguchi J, Kalka C, et al. Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration [J]. Circulation, 2002; 105(6): 732738.
9. Padilla L, Krtzsch E, Schalch P, et al. Administration of bone marrow cells into surgically induced fibrocollagenous tunnels induces angiogenesis in ischemic rat hindlimb model [J]. Microsurgery, 2003; 23(6): 568574.
10. 劉文亮, 尹邦良, 喻風雷, 等. 骨髓單個核細胞缺血組織局部移植對血運重建的影響 [J]. 中南大學學報(醫學版), 2004; 29(5): 572576.
11. Hiasa K, Ishibashi M, Ohtani K, et al. Gene transfer of stromal cellderived factor1α enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthaserelated pathway: nextgeneration chemokine therapy for therapeutic neovascularization [J]. Circulation, 2004; 109(20): 24542461.
12. Sato Y, Matsui K, Ajiki T, et al. Can a bone marrow cell contribute to organ regeneration? In vivo analysis using transgenic rats with reporter genes [J]. Transplant Proc, 2005; 37(1): 273275.
13. Otsuka H, Akashi H, Murohara T, et al. The prostacyclin analog beraprost sodium augments the efficacy of therapeutic angiogenesis induced by autologous bone marrow cells [J]. Ann Vasc Surg, 2006; 20(5): 646652.
14. de Nigris F, Balestrieri ML, WilliamsIgnarro S, et al. Therapeutic effects of autologous bone marrow cells and metabolic intervention in the ischemic hindlimb of spontaneously hypertensive rats involve reduced cell senescence and CXCR4/Akt/eNOS pathways [J]. J Cardiovasc Pharmacol, 2007; 50(4): 424433.
15. Qin SL, Li TS, Kubo M, et al. Transient increase of cytokines in the acute ischemic tissue is beneficial to cellbased therapeutic angiogenesis [J]. Circ J, 2008; 72(12): 20752080.
16. Wragg A, Mellad JA, Beltran LE, et al. VEGFR1/CXCR4positive progenitor cells modulate local inflammation and augment tissue perfusion by a SDF1dependent mechanism [J]. J Mol Med, 2008; 86(11): 12211232.
17. Iohara K, Zheng L, Wake H, et al. A novel stem cell source for vasculogenesis in ischemia: subfraction of side population cells from dental pulp [J]. Stem Cells, 2008; 26(9): 24082418.
18. Tajima H, IwaiTakano M, Yaoita H, et al. Mast cells contribute to flow restoration by bone marrow cell transplantation in rats with ischemic limbs [J]. Int Heart J, 2009; 50(2): 247257.
19. 汪忠鎬, 李震. 我國血管外科的現狀和發展 [J]. 中國普外基礎與臨床雜志, 2006; 13(6): 625628.
20. 梁翠宏. Wistar大鼠后肢缺血模型的實驗研究 [D]. 山東大學, 2005: 17.
21. 劉萬里, 薛茜, 曹明芹，等. 用 SPSS實現完全隨機設計多組比較秩和檢驗的多重比較 [J]. 地方病通報, 2007; 22(2): 2729.
22. 崔世軍，俞恒錫，滕旭，等. 家兔后肢缺血模型的制作 [J]. 中國比較醫學雜志, 2003; 13(1): 3638.
23. Heil M, Ziegelhoeffer T, Pipp F, et al. Blood monocyte concentration is critical for enhancement of collateral artery growth [J]. Am J Physiol Heart Circ Physiol, 2002; 283(6): H2411H2419.
24. 霍鑫，馮金煒，劉方峰，等. pEGFPC1/Akt體外轉染骨髓間充質干細胞對后肢缺血大鼠血管生成的影響 [J]. 中國普外基礎與臨床雜志, 2008; 15(6): 402407.
25. Iwatsuki Y, Sakata C, Kawasaki T, et al. Experimental model of lower limb ischemia in rats and the effect of YM466, an oral direct factor Xa inhibitor [J]. Biol Pharm Bull, 2007; 30(10): 18741877.
26. 梁翠宏，田鏵，徐蘊，等. 結扎切斷法與白芨微粒栓塞法建立大鼠后肢缺血模型效果比較 [J]. 山東大學學報(醫學版), 2007; 45(10): 10081010.
27. Pu LQ, Jackson S, Lachapelle KJ, et al. A persistent hindlimb ischemia model in the rabbit [J]. J Invest Surg, 1994; 7(1): 4960.
28. 梁翠宏，田鏵，徐蘊，等. 結扎切斷法制作大鼠后肢缺血模型的效果 [J]. 解剖學雜志, 2006; 29(6): 795797.
29. 楊安峰, 王平. 大鼠的解剖和組織 [M]. 北京: 科學出版社, 1980: 124130.

《中國普外基礎與臨床雜志》

結扎腹主動脈加雙側腹壁陰部動脈在大鼠后肢缺血模型中的應用

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《中國普外基礎與臨床雜志》

結扎腹主動脈加雙側腹壁陰部動脈在大鼠后肢缺血模型中的應用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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