• 1.哈爾濱醫(yī)科大學(xué)附屬第二醫(yī)院血管外科（黑龍江哈爾濱 150086）;;
  • 2.哈爾濱醫(yī)科大學(xué)附屬第二醫(yī)院內(nèi)分泌科（黑龍江哈爾濱 150086）;

目的研究外源性胰島素對(duì)糖尿病大鼠缺血后肢血管內(nèi)皮生長因子(VEGF)表達(dá)的影響及其促血管新生的作用。方法取20只健康雄性SD大鼠,將其右后肢股動(dòng)、靜脈及其分支和屬支結(jié)扎，制成糖尿病大鼠后肢缺血模型，然后將其用簡單隨機(jī)化方法隨機(jī)平均分為模型組與治療組，另取10只正常大鼠作為對(duì)照組。14 d后處死大鼠，應(yīng)用 Western blot法檢測大鼠后肢肌肉組織中VEGF蛋白表達(dá)水平，并采用堿性磷酸酶(AKP)染色法測定大鼠后肢肌肉組織中毛細(xì)血管密度。結(jié)果對(duì)照組大鼠術(shù)前和術(shù)后7 d體重和血糖水平比較差異無統(tǒng)計(jì)學(xué)意義(P gt;0.05); 模型組大鼠術(shù)后7 d與術(shù)前比較，體重明顯下降(P lt;0.05)，但血糖水平差異無統(tǒng)計(jì)學(xué)意義(P gt;0.05); 而治療組給予皮下注射胰島素注射液術(shù)后7 d較術(shù)前體重明顯下降，并且血糖水平較術(shù)前也明顯下降，差異均有統(tǒng)計(jì)學(xué)意義(P lt;0.05)。與對(duì)照組比較，治療組及模型組大鼠術(shù)后7 d體重明顯下降、血糖明顯升高(P lt;0.05，P lt;0.01); 治療組與模型組比較，體重差異無統(tǒng)計(jì)學(xué)意義(P gt;0.05)，但治療組大鼠術(shù)后7 d血糖水平較模型組明顯降低(P lt;0.05)。治療組大鼠缺血肢體肌肉組織中VEGF蛋白相對(duì)表達(dá)量(155.06±10.26)明顯高于模型組(94.30±11.23)，P lt;0.05; 對(duì)照組大鼠未檢測到VEGF蛋白表達(dá)。對(duì)照組大鼠右后肢肌肉組織中毛細(xì)血管密度明顯高于模型組和治療組(P lt;0.05)，而治療組又明顯高于模型組(P lt;0.05)。3組大鼠左后肢毛細(xì)血管密度差異無統(tǒng)計(jì)學(xué)意義(P gt;0.05); 對(duì)照組大鼠左、右后肢毛細(xì)血管密度差異無統(tǒng)計(jì)學(xué)意義(P gt;0.05); 模型組和治療組大鼠右后肢毛細(xì)血管密度均明顯低于左后肢(P lt;0.05)。結(jié)論胰島素可以增強(qiáng)糖尿病大鼠后肢缺血肌肉組織中VEGF蛋白表達(dá)，促進(jìn)毛細(xì)血管生成，發(fā)揮保護(hù)作用。

引用本文： 張英男,薛軍強(qiáng),高萍,冉繼朋. 胰島素干預(yù)對(duì)糖尿病大鼠后肢缺血的作用及意義. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(4): 391-395. doi: 復(fù)制

1. 劉仁貴, 趙紀(jì)春. 糖尿病并發(fā)下肢血管病變的發(fā)病機(jī)理及治療進(jìn)展 [J]. 中國普外基礎(chǔ)與臨床雜志, 2006, 13(6): 676679.
2. 許樟榮. 糖尿病足病變研究進(jìn)展 [J]. 中國醫(yī)師雜志, 2004, 6(1): 14.
3. 張憲生, 鄒英華, 王維亮. 纖維蛋白原與糖尿病下肢動(dòng)脈缺血性病變的關(guān)系 [J]. 中國普外基礎(chǔ)與臨床雜志, 2005, 12(4): F005.
4. Buse JB, Ginsberg HN, Bakris GL, et al. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association [J]. Circulation, 2007, 115(1): 114126.
5. 王欣, 張強(qiáng), 張宏偉, 等. 晚期糖基化終產(chǎn)物受體在糖尿病大鼠自體移植靜脈中的表達(dá)及氨基胍的干預(yù)作用 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008, 15(6): 390395.
6. 沈亞非, 徐焱成. 鏈脲佐菌素誘導(dǎo)試驗(yàn)實(shí)驗(yàn)性糖尿病大鼠模型建立的研究 [J]. 實(shí)用診斷與治療雜志, 2005, 19(2): 7980.
7. Murohara T, Asahara T, Silver M, et al. Nitric oxide synthase modulates angiogenesis in response to tissue ischemia [J]. J Clin Invest, 1998, 101(11): 25672578.
8. 喬海兵, 邢開宇. 改良?jí)A性磷酸酶染色法 [J]. 實(shí)用醫(yī)技雜志, 2006, 13(6): 10111012.
9. Abaci A, Oˇguzhan A, Kahraman S, et al. Effect of diabetes mellitus on formation of coronary collateral vessels [J]. Circulation, 1999, 99(17): 22392242.
10. Benjamin LE. Glucose, VEGFA and diabetic complications [J]. Am J Pathol, 2001, 158(4): 11811184.
11. 陶蕊, 徐蓉, 段俊麗, 等. 高血糖狀態(tài)對(duì)缺血后血管新生影響的機(jī)制研究 [J]. 上海交通大學(xué)學(xué)報(bào)(醫(yī)學(xué)版), 2008, 28(5): 492496.
12. Dandona P, Mohanty P, Chaudhuri A, et al. Insulin infusion in acute illness [J]. J Clin Invest, 2005, 115(8): 20692072.
13. Langouche L, Vanhorebeek I, Vlasselaers D, et al. Intensive insulin therapy protects the endothelium of critically ill patients [J]. J Clin Invest, 2005, 115(8): 22772286.
14. 馬衛(wèi)國, 朱本章. 胰島素抗炎作用研究進(jìn)展 [J]. 國外醫(yī)學(xué)內(nèi)分泌學(xué)分冊(cè), 2004, 24(3): 194196.
15. Garg R, Chaudhuri A, Munschauer F, et al. Hyperglycemia, insulin, and acute ischemic stroke: a mechanistic justification for a trial of insulin infusion therapy [J]. Stroke, 2006, 37(1): 267273.
16. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes [J]. J Clin Invest, 2005, 115(5): 11111119.
17. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease [J]. N Engl J Med, 2005, 352(16): 16851695.
18. 趙春華. 干細(xì)胞原理、技術(shù)與臨床 [M]. 北京: 化學(xué)工業(yè)出版社, 2006: 177178.
19. 陳毅, 劉丹萍. 三種細(xì)胞因子體外聯(lián)合誘導(dǎo)兔骨髓間充質(zhì)干細(xì)胞向血管內(nèi)皮細(xì)胞的分化 [J]. 中國組織工程研究與臨床康復(fù), 2008, 12(21): 40934096.
20. 劉元標(biāo). 血管內(nèi)皮生長因子與血管新生 [J]. 中國康復(fù)醫(yī)學(xué)雜志, 2004, 19(5): 396400.
21. Yamagishi S, Abe R, Jinnouchi Y, et al. Pigment epitheliumderived factor inhibits vascular endothelial growth factorinduced vascular hyperpermeability both in vitro and in vivo [J]. Int Med Res, 2007, 35(6): 896899.
22. Takeshita S, Isshiki T, Ochiai M, et al. Endotheliumdependent relaxation of collateral microvessels after intramuscular gene transfer of vascular endothelial growth factor in a rat model of hindlimb ischemia [J]. Circulation, 1998, 98(13): 12611263.
23. Gerber HP, McMurtrey A, Kowalski J, et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3’kinase/Akt signal transduction pathway. Requirement for Flk1/KDR activation [J]. J Biol Chem, 1998, 273(46): 3033630343.
24. Hattori K, Dias S, Heissig B, et al. Vascular endothelial growth factor and angiopoietin1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells [J]. J Exp Med, 2001, 193(9): 10051014.
25. 吳星火, 楊述華, 王晶, 等. 胰島素對(duì)脊髓損傷后血管內(nèi)皮生長因子的表達(dá)及血管再生的影響 [J]. 創(chuàng)傷外科雜志, 2006, 8(5): 452455.
26. Neufeld G, Cohen T, Gengrinovitch S, et al. Vascular endothelial growth factor (VEGF) and its receptors [J]. FASEB J, 1999, 13(1): 922.
27. Jiang ZY, He Z, King BL, et al. Characterization of multiple signaling pathways of insulin in the regulation of vascular endothelial growth fact or expression in vascular cells and angiogenesis [J]. J Biol Chem, 2003, 278(34): 3196431971.
28. Smith LE, Shen W, Perruzzi C, et al. Regulation of vascular endothelial growth factordependent retinal neovascularization by insulinlike growth factor1 receptor [J]. Nat Med, 1999, 5(12): 13901395.
  1. 1. 劉仁貴, 趙紀(jì)春. 糖尿病并發(fā)下肢血管病變的發(fā)病機(jī)理及治療進(jìn)展 [J]. 中國普外基礎(chǔ)與臨床雜志, 2006, 13(6): 676679.
  2. 2. 許樟榮. 糖尿病足病變研究進(jìn)展 [J]. 中國醫(yī)師雜志, 2004, 6(1): 14.
  3. 3. 張憲生, 鄒英華, 王維亮. 纖維蛋白原與糖尿病下肢動(dòng)脈缺血性病變的關(guān)系 [J]. 中國普外基礎(chǔ)與臨床雜志, 2005, 12(4): F005.
  4. 4. Buse JB, Ginsberg HN, Bakris GL, et al. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association [J]. Circulation, 2007, 115(1): 114126.
  5. 5. 王欣, 張強(qiáng), 張宏偉, 等. 晚期糖基化終產(chǎn)物受體在糖尿病大鼠自體移植靜脈中的表達(dá)及氨基胍的干預(yù)作用 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008, 15(6): 390395.
  6. 6. 沈亞非, 徐焱成. 鏈脲佐菌素誘導(dǎo)試驗(yàn)實(shí)驗(yàn)性糖尿病大鼠模型建立的研究 [J]. 實(shí)用診斷與治療雜志, 2005, 19(2): 7980.
  7. 7. Murohara T, Asahara T, Silver M, et al. Nitric oxide synthase modulates angiogenesis in response to tissue ischemia [J]. J Clin Invest, 1998, 101(11): 25672578.
  8. 8. 喬海兵, 邢開宇. 改良?jí)A性磷酸酶染色法 [J]. 實(shí)用醫(yī)技雜志, 2006, 13(6): 10111012.
  9. 9. Abaci A, Oˇguzhan A, Kahraman S, et al. Effect of diabetes mellitus on formation of coronary collateral vessels [J]. Circulation, 1999, 99(17): 22392242.
  10. 10. Benjamin LE. Glucose, VEGFA and diabetic complications [J]. Am J Pathol, 2001, 158(4): 11811184.
  11. 11. 陶蕊, 徐蓉, 段俊麗, 等. 高血糖狀態(tài)對(duì)缺血后血管新生影響的機(jī)制研究 [J]. 上海交通大學(xué)學(xué)報(bào)(醫(yī)學(xué)版), 2008, 28(5): 492496.
  12. 12. Dandona P, Mohanty P, Chaudhuri A, et al. Insulin infusion in acute illness [J]. J Clin Invest, 2005, 115(8): 20692072.
  13. 13. Langouche L, Vanhorebeek I, Vlasselaers D, et al. Intensive insulin therapy protects the endothelium of critically ill patients [J]. J Clin Invest, 2005, 115(8): 22772286.
  14. 14. 馬衛(wèi)國, 朱本章. 胰島素抗炎作用研究進(jìn)展 [J]. 國外醫(yī)學(xué)內(nèi)分泌學(xué)分冊(cè), 2004, 24(3): 194196.
  15. 15. Garg R, Chaudhuri A, Munschauer F, et al. Hyperglycemia, insulin, and acute ischemic stroke: a mechanistic justification for a trial of insulin infusion therapy [J]. Stroke, 2006, 37(1): 267273.
  16. 16. Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes [J]. J Clin Invest, 2005, 115(5): 11111119.
  17. 17. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease [J]. N Engl J Med, 2005, 352(16): 16851695.
  18. 18. 趙春華. 干細(xì)胞原理、技術(shù)與臨床 [M]. 北京: 化學(xué)工業(yè)出版社, 2006: 177178.
  19. 19. 陳毅, 劉丹萍. 三種細(xì)胞因子體外聯(lián)合誘導(dǎo)兔骨髓間充質(zhì)干細(xì)胞向血管內(nèi)皮細(xì)胞的分化 [J]. 中國組織工程研究與臨床康復(fù), 2008, 12(21): 40934096.
  20. 20. 劉元標(biāo). 血管內(nèi)皮生長因子與血管新生 [J]. 中國康復(fù)醫(yī)學(xué)雜志, 2004, 19(5): 396400.
  21. 21. Yamagishi S, Abe R, Jinnouchi Y, et al. Pigment epitheliumderived factor inhibits vascular endothelial growth factorinduced vascular hyperpermeability both in vitro and in vivo [J]. Int Med Res, 2007, 35(6): 896899.
  22. 22. Takeshita S, Isshiki T, Ochiai M, et al. Endotheliumdependent relaxation of collateral microvessels after intramuscular gene transfer of vascular endothelial growth factor in a rat model of hindlimb ischemia [J]. Circulation, 1998, 98(13): 12611263.
  23. 23. Gerber HP, McMurtrey A, Kowalski J, et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3’kinase/Akt signal transduction pathway. Requirement for Flk1/KDR activation [J]. J Biol Chem, 1998, 273(46): 3033630343.
  24. 24. Hattori K, Dias S, Heissig B, et al. Vascular endothelial growth factor and angiopoietin1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells [J]. J Exp Med, 2001, 193(9): 10051014.
  25. 25. 吳星火, 楊述華, 王晶, 等. 胰島素對(duì)脊髓損傷后血管內(nèi)皮生長因子的表達(dá)及血管再生的影響 [J]. 創(chuàng)傷外科雜志, 2006, 8(5): 452455.
  26. 26. Neufeld G, Cohen T, Gengrinovitch S, et al. Vascular endothelial growth factor (VEGF) and its receptors [J]. FASEB J, 1999, 13(1): 922.
  27. 27. Jiang ZY, He Z, King BL, et al. Characterization of multiple signaling pathways of insulin in the regulation of vascular endothelial growth fact or expression in vascular cells and angiogenesis [J]. J Biol Chem, 2003, 278(34): 3196431971.
  28. 28. Smith LE, Shen W, Perruzzi C, et al. Regulation of vascular endothelial growth factordependent retinal neovascularization by insulinlike growth factor1 receptor [J]. Nat Med, 1999, 5(12): 13901395.