目的 通過線栓法制備大鼠慢性后肢缺血模型,將其與急性后肢缺血模型進(jìn)行比較研究。
方法 采用線栓法制備Lewis大鼠慢性后肢缺血模型,分別于術(shù)后第7、14、28、42及49天進(jìn)行激光多普勒血流分析及血管造影。每組動物在血管造影后處死,分別取其健側(cè)和患側(cè)股四頭肌和腓腸肌行HE染色及α-actin免疫組織化學(xué)染色,并計(jì)算小動脈密度。
結(jié)果 慢性后肢缺血模型組動物術(shù)后未出現(xiàn)明顯的跛行和肢體壞死。血流分析發(fā)現(xiàn),慢性后肢缺血模型在術(shù)后第49天仍處于缺血狀態(tài)。后肢肌肉組織病理學(xué)檢查未發(fā)現(xiàn)急性壞死和肌肉纖維化的表現(xiàn)。術(shù)后第7天,慢性缺血組股四頭肌的小動脈密度低于急性缺血組(0.015 2比0.036 4)。
結(jié)論 線栓法制備大鼠慢性后肢缺血模型與目前采用的急性動物后肢缺血模型制備方法有顯著的不同, 其缺血肢體較少受到代償機(jī)制的影響且缺血時(shí)間維持較長,此為進(jìn)一步研究缺血后血管新生的機(jī)理和治療嚴(yán)重的下肢缺血提供了一種新的動物模型。
引用本文: 楊盛家,陳兵,羅濤,佟鑄,張淑文,史小林,許晴,張斌,張建. Lewis大鼠慢性后肢缺血模型的制備與評價(jià)△. 中國普外基礎(chǔ)與臨床雜志, 2012, 19(12): 1291-1297. doi: 復(fù)制
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2. | van Royen N, Hoefer I, Bottinger M, et al. Local monocytechemoattractant protein-1 therapy increases collateral artery formationin apolipoprotein E-deficient mice but induces systemic monocytic CD11b expression, neointimal formation, and plaque progression[J]. Circ Res, 2003, 92(2):218-225. |
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4. | Taniyama Y, Morishita R, Aoki M, et al. Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models:preclinical study for treatment of peripheral arterial disease[J]. Gene Ther, 2001, 8(3):181-189. |
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6. | Shyu KG, Manor O, Magner M, et al. Direct intramuscularinjection of plasmid DNA encoding angiopoietin-1 but notangiopoietin-2 augments revascularization in the rabbit ischemic hindlimb[J]. Circulation, 1998, 98(19):2081-2087. |
7. | Chang DS, Su H, Tang GL, et al. Adeno-associated viral vector-mediated gene transfer of VEGF normalizes skeletal muscleoxygen tension and induces arteriogenesis in ischemic rat hindlimb[J]. Mol Ther, 2003, 7(1):44-51. |
8. | Brevetti LS, Chang DS, Tang GL, et al. Overexpression of endothelial nitric oxide synthase increases skeletal muscle blood flow and oxygenation in severe rat hindlimb ischemia[J]. J Vasc Surg, 2003, 38(4):820-826. |
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10. | Aviles RJ, Annex BH, Lederman RJ, et al. Testing clinical therapeutic angiogenesis using basic fibroblast growth factor (FGF-2)[J]. Br J Pharmacol, 2003, 140(4):637-646. |
11. | Rajagopalan S, Mohler ER 3rd, Lederman RJ, et al. Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease:a phaseⅡrandomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor121 in patients with disabling intermittent claudication[J].Circulation, 2003, 108(16):1933-1938. |
12. | 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. |
13. | Couffinhal T, Silver M, Zheng LP, et al . Mouse model ofangiogenesis[J]. Am J Pathol, 1998, 152(6):1667-1679. |
14. | Ito WD, Arras M, Scholz D, et al. Angiogenesis but not collateral growth is associated with ischemia after femoral artery occlusion[J]. Am J Physiol , 1997, 273(3 Pt 2):H1255-H1265. |
15. | 楊盛家, 陳兵, 羅濤, 等. 大鼠后肢急性缺血模型的構(gòu)建與評估[J]. 中國普通外科雜志, 2009, 18(6):580-583. |
16. | 梁翠宏, 田鏵, 徐蘊(yùn), 等. 結(jié)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(xué)學(xué)報(bào), 2007, 45(10):1008-1015. |
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19. | 劉坤, 楊琨, 羅軍, 等. 結(jié)扎腹主動脈加雙側(cè)腹壁陰部動脈在大鼠后肢缺血模型中的應(yīng)用[J]. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(3):258-262. |
20. | 楊盛家, 陳兵, 佟鑄, 等. 應(yīng)用激光多普勒血流儀對大鼠后肢缺血模型血流動力學(xué)的觀察[J]. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(3):137-140. |
21. | Topper JN, Gimbrone MA Jr. Blood flow and vascular gene expression:fluid shear stress as a modulator of endothelial phenotype[J] . Mol Med Today, 1999, 5(1):40-46. |
22. | Garcia-Cardena G, Comander J, Anderson KR, et al. Biomechanical activation of vascular endothelium as a determinant of its functional phenotype[J] . Proc Natl Acad Sci U S A, 2001, 98(8):4478-4485. |
23. | Buschmann IR, Hoefer IE, van Royen N, et al. GM-CSF:a strong arteriogenic factor acting by amplification of monocyte function[J] . Atherosclerosis, 2001, 159(2):343-356. |
24. | van Royen N, Hoefer I, Buschmann I, et al. Effects of local MCP-1 protein therapy on the development of the collateral circulation and atherosclerosis in Watanabe hyperlipidemic rabbits[J]. Cardiovasc Res, 2003, 57(1):178-185. |
- 1. Schainfeld RM, Isner JM. Critical limb ischemia:nothing to give at the office?[J]. Ann Intern Med, 1999, 130(5):442-444.
- 2. van Royen N, Hoefer I, Bottinger M, et al. Local monocytechemoattractant protein-1 therapy increases collateral artery formationin apolipoprotein E-deficient mice but induces systemic monocytic CD11b expression, neointimal formation, and plaque progression[J]. Circ Res, 2003, 92(2):218-225.
- 3. Takeshita S, Tsurumi Y, Couffinahl T, et al. Gene transfer of naked DNA encoding for three isoforms of vascular, endothelial growth factor stimulates collateral development in vivo[J]. Lab Invest, 1996, 75(4):487-501.
- 4. Taniyama Y, Morishita R, Aoki M, et al. Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models:preclinical study for treatment of peripheral arterial disease[J]. Gene Ther, 2001, 8(3):181-189.
- 5. Paek R, Chang DS, Brevetti LS, et al. Correlation of a simple direct measurement of muscle pO2 to a clinical ischemia index and histology in a rat model of chronic severe hindlimb ischemia[J] . J Vasc Surg , 2002, 36(1):172-179.
- 6. Shyu KG, Manor O, Magner M, et al. Direct intramuscularinjection of plasmid DNA encoding angiopoietin-1 but notangiopoietin-2 augments revascularization in the rabbit ischemic hindlimb[J]. Circulation, 1998, 98(19):2081-2087.
- 7. Chang DS, Su H, Tang GL, et al. Adeno-associated viral vector-mediated gene transfer of VEGF normalizes skeletal muscleoxygen tension and induces arteriogenesis in ischemic rat hindlimb[J]. Mol Ther, 2003, 7(1):44-51.
- 8. Brevetti LS, Chang DS, Tang GL, et al. Overexpression of endothelial nitric oxide synthase increases skeletal muscle blood flow and oxygenation in severe rat hindlimb ischemia[J]. J Vasc Surg, 2003, 38(4):820-826.
- 9. Lederman RJ, Mendelsohn FO, Anderson RD,?et al. Therapeuticangiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (the TRAFFIC study):a randomised trial[J]. Lancet, 2002, 359(9323):2053-2058.
- 10. Aviles RJ, Annex BH, Lederman RJ, et al. Testing clinical therapeutic angiogenesis using basic fibroblast growth factor (FGF-2)[J]. Br J Pharmacol, 2003, 140(4):637-646.
- 11. Rajagopalan S, Mohler ER 3rd, Lederman RJ, et al. Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease:a phaseⅡrandomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor121 in patients with disabling intermittent claudication[J].Circulation, 2003, 108(16):1933-1938.
- 12. 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.
- 13. Couffinhal T, Silver M, Zheng LP, et al . Mouse model ofangiogenesis[J]. Am J Pathol, 1998, 152(6):1667-1679.
- 14. Ito WD, Arras M, Scholz D, et al. Angiogenesis but not collateral growth is associated with ischemia after femoral artery occlusion[J]. Am J Physiol , 1997, 273(3 Pt 2):H1255-H1265.
- 15. 楊盛家, 陳兵, 羅濤, 等. 大鼠后肢急性缺血模型的構(gòu)建與評估[J]. 中國普通外科雜志, 2009, 18(6):580-583.
- 16. 梁翠宏, 田鏵, 徐蘊(yùn), 等. 結(jié)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(xué)學(xué)報(bào), 2007, 45(10):1008-1015.
- 17. Tang GL, Chang DS, Sarkar R, et al. The effect of gradual or acute arterial occlusion on skeletal muscle blood flow, arteriogenesis, and inflammation in rat hindlimb ischemia[J] . J Vasc Surg, 2005, 41(2):312-320.
- 18. Baffour R, Garb JL, Kaufman J, et al. Angiogenic therapy for the chronically ischemic lower limb in a rabbit model[J] . J Surg Res, 2000, 93(2):219-229.
- 19. 劉坤, 楊琨, 羅軍, 等. 結(jié)扎腹主動脈加雙側(cè)腹壁陰部動脈在大鼠后肢缺血模型中的應(yīng)用[J]. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(3):258-262.
- 20. 楊盛家, 陳兵, 佟鑄, 等. 應(yīng)用激光多普勒血流儀對大鼠后肢缺血模型血流動力學(xué)的觀察[J]. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(3):137-140.
- 21. Topper JN, Gimbrone MA Jr. Blood flow and vascular gene expression:fluid shear stress as a modulator of endothelial phenotype[J] . Mol Med Today, 1999, 5(1):40-46.
- 22. Garcia-Cardena G, Comander J, Anderson KR, et al. Biomechanical activation of vascular endothelium as a determinant of its functional phenotype[J] . Proc Natl Acad Sci U S A, 2001, 98(8):4478-4485.
- 23. Buschmann IR, Hoefer IE, van Royen N, et al. GM-CSF:a strong arteriogenic factor acting by amplification of monocyte function[J] . Atherosclerosis, 2001, 159(2):343-356.
- 24. van Royen N, Hoefer I, Buschmann I, et al. Effects of local MCP-1 protein therapy on the development of the collateral circulation and atherosclerosis in Watanabe hyperlipidemic rabbits[J]. Cardiovasc Res, 2003, 57(1):178-185.