我们的网站为什么显示成这样？

可能因为您的浏览器不支持样式，您可以更新您的浏览器到最新版本，以获取对此功能的支持，访问下面的网站，获取关于浏览器的信息：

|本期目录/Table of Contents|

脉冲电磁场对糖尿病大鼠急性下肢缺血模型血管再生的作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2010年第3期
页码:
338-343
栏目:
基础研究
出版日期:
2010-04-06

文章信息/Info

Title:
Effects of pulsed electromagnetic fields on acute hindlimb ischemic diabetic rats in microcirculation angiogenesis
作者:
潘云虎; 李飞; 陈江红; 张申伟; 郭文怡
第四军医大学西京医院心血管内科,陕西 西安 710032
Author(s):
PAN Yun-hu;  LI Fei;  CHEN Jiang-hong;  ZHANG Shen-wei;  GUO Wen-yi
Department of Cardiovasology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
关键词:
脉冲电磁场; 下肢缺血; 血管再生; CD31; FGF-2; 大鼠
Keywords:
pulsed electromagnetic fields;  hindlimb ischemia;  angiogenesis;  CD31;  FGF-2;  rat
分类号:
R543　
DOI:
-
文献标识码:
A
摘要:
目的: 探讨脉冲电磁场(PEMF)对糖尿病大鼠急性下肢缺血模型血管再生的作用。方法: 60只SD大鼠按照60 mg/kg腹腔注射链脲菌素(STZ)，建立糖尿病大鼠模型后，再根据文献Kawasaki等［2］的方法建立大鼠急性下肢缺血模型，并随机分为实验组和对照组,每组30只。实验组术后第1天，即给予PEMF治疗（每天2 h，共28 d），对照组不做任何处理。于术后当天及术后7、14、28 d，运用激光多普勒技术检测血流。并在术后7、14、28 d处死动物（每组每次处死10只），分离缺血后肢的肌肉，采用免疫组织化染色法检测CD31的表达；采用Western-blot法检测VEGF、FGF-2、VEGFR2、FGFR1、ERK1/2、P-ERK1/2、P38及P-P38的表达。结果: 激光多普勒检查显示，实验组在术后14、28 d，血流的恢复（0.64±0.02、0.85±0.02）明显高于对照组（0.48±0.02、0.61±0.02，P<0.01)。实验组术后14、28 d，CD31的表达(677.4±15.6)/mm2和(837.2±25.6)/mm2明显高于对照组(495.2±25.3)/mm2和(619.4±19.2)/mm2(P<0.01）。Western blot法检测在各个时间段的FGF-2和FGFR1的表达实验组均高于对照组(P<0.05)；而VEGF及其受体的表达无明显差异。实验组P-ERK1/2与T-ERK1/2的比值在各个时间段均高于对照组（P<0.05）,两组P-P38与T-P38的比值无显著性差异。结论: PEMF可促进糖尿病大鼠急性下肢缺血的血管新生，机制可能为通过刺激血管内皮细胞释放FGF-2，并与ERK1/2有关，因ERK1/2是FGF-2促进血管增生的重要信号转导途径。
Abstract:
AIM: To observe the effects of pulsed electromagnetic fields (PEMF) on acute hindlimb ischemic diabetic rats in microcirculation angiogenesis. METHODS: Sixty male Sprague Dawley diabetic rats were randomly divided into experimental group (n=30）and control group (n=30) and acute hindlimb ischemia models were established in all rats. After operation, rats in the experimental group were exposed to PEMFs for 2 h each day, whereas rats in the control group were not given any treatment. Laser-Doppler perfusion measurements were used to determine the blood flow of hindlimb ischemia on postoperative days0, 7, 14 and 28, and immunohistochemical analysis of CD31 was used to evaluate the changes in angiogenesis. Levels of VEGF, FGF-2, VEGFR2, FGFR1, ERK1/2, P-ERK1/2, P38 and P-P38 levels were determined by Western blot analysis in ischemic skeletal muscle on postoperative days 7, 14 and 28. RESULTS: Perfusion ratios were significantly higher in PEMF-treated diabetic rats at days 14 and 28 compared with controls (0.64±0.02 vs.0.48±0.02, P<0.01); (0.85±0.02 vs.0.61±0.02, P<0.01). CD31 density in tissues measured by immunohistochemistry significantly increased in PEMF-treated groups on days 14 and 28 ［(677.4±15.6) vs.(495.2±25.3)/mm2, P<0.01; (837.2±25.6) vs.(619.4±19.2)/mm2, P<0.01］. Levels of FGF-2 and FGFR1 in ischemic hindlimbs significantly increased in PEMF group at all timepoints, as well as p-ERK1/2 and total ERK1/2. No significant differences were observed in VEGF, VEGFR2 and p-p38/total p38 between groups. CONCLUSION: PEMFs promote angiogenesis in diabetes by upregulation of FGF-2. As an indispensable signal pathway for FGF2-induced angiogenesis, ERK is responsible for coupling FGFR1 to multiple downstream pathways to mediate blood vessel formation. PEMFs can be used in the prevention and treatment of lower limb ischemia in diabetic patients.

参考文献/References

［1］ Yen-pattor GP, Patton WF, Beer DM, et al. Endothelial cell response to pulsed electromagnetic fields: stimulation of growth rate and angiogenesis in vitro［J］. J cell physiol, 1988, 134(1):37-46．

［2］Kawasaki K, Smith RS Jr, Hsieh CM, et al. Activation of the phosphatidylinositol 3-kinase/protein kinase Akt pathway mediates nitric oxide-induced endothelial cell migration and angiogenesis［J］. Mol Cell Biol, 2003, 23(16)：5726-5737．

［3］ Nakae M, Kamiya H, Naruse K, et al. Effects of basic fibroblast growth factor on experimental diabetic neuropathy in rats［J］. Diabetes, 2006, 55(5):1470-1477．

［4］Tepper OM, Callaghan MJ, Chang EI, et al. Electromagnetic fields increase in vitro and in vivo angiogenesis through endothelial release of FGF-2［J］. FASEB J, 2004, 18(11):1231-1233．

［5］ Gao F, Gao E, Yue TL, et al. Nitric oxide mediates the antiapoptotic effect of insulin in myocardial ischemia-reperfusion: the roles of PI3-kinase, Akt, and endothelial nitric oxide synthase phosphorylation［J］. Circulation, 2002, 105(12):1497-1502.

［6］King H, Aubert RE, Herman WH. Global burden of diabetes 1995-2025: prevalence, numerical estimates, and projections［J］. Diabetes Care, 1998, 21(9):1414-1431.

［7］Kaio E, Tanaka S, Kitadai Y, et al. Clinical significance of angiogenic factor expression at the deepest invasive site of advanced colorectal carcinoma［J］. Oncology, 2003, 64(1):61-73．

［8］ Furudoi A, Tanaka S, Haruma K, et al. Clinical significance of vascular endothelial growth factor C expression and angiogenesis at the deepest invasive site of advanced colorectal carcinoma［J］. Oncology, 2002, 62 (2):157-166.

［9］Lang I, Hoffmann C, Olip H, et al. Differential mitogenic responses of human microvascular and microvascular endothelial cells to cytokines underline their phenotypic heterogeneity［J］. Cell Prolif, 2001, 34(3):143-155．

［10］Trivier E, Kurz DJ, Hong Y, et al. Differential regulation of telomerase in endothelial cells by fibroblast growth factor-2 and vascular endothelial growth factor-a: association with replicative life span［J］. Ann N Y Acad Sci, 2004, 1019:111-115．

[11]Callaghan MJ, Chang EI, Seiser N, et al. Pulsed electromagnetic fields accelerate normal and diabetic wound healing by increasing endogenous FGF-2 release［J］. Plast Reconstr Surg, 2008, 121(1):130-141．

[12]Brighton CT, Wang W, Seldes R, et al. Signal transduction in electrically stimulated bone cells［J］. J Bone Joint Surg Am, 2001, 83(10):1514-1523．

[13]Nie K, Henderson A. MAP kinase activation in cells exposed to a 60 Hzelectromagneticfield［J］. JCellBiochem,2003,90(6):1197-1206．

[14]Phillips JL. Effects of electromagnetic field exposure on gene transcription［J］. J Cell Biochem, 1993, 51(4)：381-386．

[15]Chen Z, Gibson TB, Robinson F, et al. MAP kinases［J］. Chem Rev, 2001, 101(8):2449-2476.

［16］Pearson G, Robinson F, Beers Gibson T, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions［J］. Endocr Rev, 2001, 22(2):153-183.

备注/Memo

备注/Memo:
收稿日期：2009-09-23.基金项目：国家自然科学基金项目资助(30672368) 通讯作者：郭文怡，教授， 主要从事冠心病介入治疗的研究Email:guowenyi@tom.com 作者简介：潘云虎，硕士生Email:pyh92yy@yahoo.com.cn
更新日期/Last Update: 2010-04-09