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外源性HGF基因转染对肺动脉高压兔肺血流灌注及肺动脉压力的影响 被引量:4

Effect of exogenous HGF gene transfection on pulmonary perfusion and pressure in pulmonary artery hypertension in rabbits
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摘要 目的:探讨外源性肝细胞生长因子(HGF)基因转染高动力性肺动脉高压家兔后促进侧支肺血管生成、改善肺血流灌注、降低肺动脉压力的可行性。方法:将肺动脉高压兔随机分为对照组、空病毒组和HGF基因转染组;HGF基因转染组经气管内滴入法转染Ad-HGF,对照组和空病毒组分别气管内滴入同体积PBS液和Ade-no-Null;4周后,通过MacLab/8s多功能生理仪行血流动力学检测,通过抗FⅧ+α-SMA抗体免疫荧光双标检测肺小动脉密度、FITC-lectin灌注+抗α-SMA荧光双标记了解肺血管灌注情况。结果:气管内给药4周后,HGF基因治疗组含平滑肌细胞的小动脉密度较肺动脉高压对照组和空病毒组(12.5±2.7)/mm2明显增多(P<0.05);HGF组肺血流灌注获得有效改善,而肺动脉高压对照组和空病毒转染组肺血管仍处于狭窄甚至闭塞状态;HGF治疗组肺动脉平均压明显低于肺动脉高压对照组和空病毒转染组(P<0.05)。结论:肺动脉高压模型动物经气管滴入法转染外源性HGF,可以促进肺侧支血管生成,增加肺灌注并有效降低肺动脉压力。 AIM: To investigate the feasibility of exogenous hepatocyte growth factor(HGF) gene transfection to promote pulmonary collateral angiogenesis,improve pulmonary perfusion and reduce pulmonary artery pressure in the rabbit model of pulmonary artery hypertension(PAH).METHODS: The model rabbits of PAH were randomly divided into control group,empty vector group and HGF gene transfection group.The rabbits in HGF gene transfection group were transfected with Ad-HGF via intratracheal instillation.Pulmonary hemodynamic indicators were monitored in the 4th week after HGF gene transfection.Density of pulmonary vessels was examined with double-labeling immunofluorescence(endothelial cells were labeled with anti-FⅧ and vascular smooth muscle cells were marked with anti-α-SMA).Double-labeling immunofluorescence of FITC-lectin and anti-α-SMA was also performed to evaluate the pulmonary blood perfusion.RESULTS: Four weeks after transfection,the density of pulmonary arterioles of the rabbits in HGF gene transfection group was higher than that in control group and empty vector group(P0.05),which was confirmed by double-labeling immunofluorescence.Pulmonary blood perfusion in HGF group was significantly increased compared with that in the other two groups,in which pulmonary arterial stenosis and occlusion were observed.The mean pulmonary artery pressure in HGF transfection group was much lower than that in control group and empty vector group(P0.05). CONCLUSION: Four weeks after intratracheal adenoviral-mediated HGF gene transfection,pulmonary collateral vessels and pulmonary perfusion increase,and the pulmonary artery pressure is effectively reduced.
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2011年第11期2217-2220,2224,共5页 Chinese Journal of Pathophysiology
基金 国家自然科学基金资助项目(No.30571845) 江苏省自然科学基金资助项目(No.BK2007033) 江苏省高校自然科学基金资助项目(No.07KJD310218) 徐州市科技计划项目(No.XM09B072)
关键词 肝细胞生长因子 血管新生 基因治疗 肺动脉高压 Hepatocyte growth factors Angiogenesis Gene therapy Pulmonary artery hypertension
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参考文献10

  • 1Duffels M,van Loon L,Berger R,et al.Pulmonary arterial hypertension associated with a congenital heart defect:advanced medium-term medical treatment stabilizes clinical condition[J].Congenit Heart Dis,2007,2(4):242-249.
  • 2Roos-hesselink JW,Meijboom FJ,Spitaels SE,et al.Outcome of patients after surgical closure of ventricular septal defect at young age:longitudinal follow-up of 22-34 years[J].Eur Heart J,2004,25(12):1057-1062.
  • 3Azuma J,Taniyama Y,Takeya Y,et al.Angiogenic and antifibrotic actions of hepatocyte growth factor improve cardiac dysfunction in porcine ischemic cardiomyopathy[J].Gene Ther,2006,13(16):1206-1213.
  • 4Funatsu T,Sawa Y,Ohtake S,et al.Therapeutic angiogenesis induced by myocardial injection of naked cDNA plasmid encoding hepatocyte growth factor in ischemic canine heart[J].J Thorac Cardiovasc Surg,2002,124(6):1099-1105.
  • 5王伟,张宜乾,吴树明.兔高动力性肺动脉高压模型的建立[J].中国病理生理杂志,2006,22(3):612-613. 被引量:4
  • 6Nagumo K,Yamaki S,Takahashi T.Extremely thickened media of small pulmonary arteries in fatal pulmonary hypertension with congenital heart disease:a morphometric and clinicopathological study[J].Jpn Circ J,2000,64(12):909-914.
  • 7Morishita R,Aoki M,Hashiya N,et al.Safety evaluation of clinical gene therapy using hepatocyte growth factor to treat peripheral arterial disease[J].Hypertension,2004,44(2):203-209.
  • 8Taniyama Y,Morishita R,Hiraoka K,et al.Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat diabetic hind limb ischemia model:molecular mechanisms of delayed angiogenesis in diabetes[J].Circulation,2001,104(19):2344-2350.
  • 9王伟,吴树明,张中明,张宜乾.经气管/静脉途径行肺脏腺病毒载体基因转染的效率和毒性分析[J].中国病理生理杂志,2008,24(12):2493-2496. 被引量:3
  • 10Yuan JX,Rubin LJ.Pathogenesis of pulmonary arterial hypertension:the need for multiple hits[J].Circulation,2005,111(5):534-538.

二级参考文献18

  • 1程昊钰,何明生,王廷华,张洪钿,王熙才,伍治平,王方方,刘鲲,黄桂琴,胡艳丽.绿色荧光蛋白转基因小鼠CD34^+/CD45^+细胞在脊髓全横断大鼠模型中的存活及迁移[J].中国病理生理杂志,2007,23(3):579-583. 被引量:4
  • 2Champion HC, Bivalacqua TJ, Greenberg SS, et al. Adenoviral gene transfer of endothelial nitric - oxide synthase (eNOS) partially restores normal pulmonary arterial pressure in eNOS - deficient mice [ J ]. Proc Natl Acad Sci USA ,2002,99 (20) : 13248 - 13253.
  • 3Zhao YD, Courtman DW, Deng Y,et al. Rescue of monocrotaline- induced pulmonary arterial hypertension using bone marrow - derived endothelial - like progenitor cells. efficacy of combined cell and eNOS gene therapy in established disease[J] . Circ Res, 2005,96(4) :442 -450.
  • 4Rex TS, Peet JA, Surace EM, et al. The distribution, concentration, and toxicity of enhanced green fluorescent protein in retinal cells after genomie or somatic ( virus - mediated) gene transfer[ J]. Mol Vis,2005,11 : 1236 - 1245.
  • 5Liu Q, Muruve DA. Molecular basis of the inflammatory response to adenovirus vectors [ J ]. Gene Ther, 2003,10 (11) :935 -940.
  • 6Catalucci D, Sporeno E, Cirillo A, et al. an Adenovirus type 5 (AdS) amplicon -based packaging cell line for production of high - capacity helper - independent delta E1 - E2 - E3 - FA AdS vectors[ J]. J Virol, 2005, 79(10) : 6400-6409.
  • 7Hendel RC, Henry TD, Rocha - Singh K, et al. Effect of intracoronary recombinant human vascular endothelial growth factor on myocardial perfusion: evidence for a dose - dependent effect [ J ]. Circulation, 2000, 101 ( 2 ) : 118 - 121.
  • 8Ni S, Bernt K, Gaggar A, et al. Evaluation of biodistribution and safety of adenocirus vectors containing group B fibers after intravenous injection into baboons [J]. Hum Gene Ther,2005,16(6) :664 -677.
  • 9Ono M, Sawa Y, Matsumoto K, et al. In vivo gene transfection with hepatocyte growth factor via the pulmonary artery induces angiogenesis in the rat lung [ J ]. Circulation, 2002,106(12 Suppl 1) :I264 -I269.
  • 10Partovian C, Adnot S, Raffestin B, et al. Adenovirus - mediated lung vascular endothelial growth factor overexpression protects against hypoxic pulmonary hypertension in rats[J]. Am J Respir Cell Mol Biol, 2000, 23(6) : 762 - 771.

共引文献5

同被引文献74

  • 1周一军,王佳贺,张锦.肝细胞生长因子抗糖基化终产物诱导内皮细胞凋亡及分子机制[J].中国医科大学学报,2006,35(4):367-370. 被引量:3
  • 2Humbert M, Morrell NW, Archer SL, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension [ J]. J Am Coil Cardiol,2004, 43 (12 Suppl S) :13S-24S.
  • 3Stenmark KR, Rabinovitch M. Emerging therapies for the treatment of pulmonary hypertension[ J ]. Pediatr Crit Care Med, 2010,11 (2 Suppl) : S85-S90.
  • 4Wu J, Lei MX, Xie XY, et al. Rosiglitazone inhibits high glucose-induced apoptosis in human umbilical vein endo- thelial cells through the PI3K/Akt/eNOS pathway [ J]. Can J Physiol Pharmacol, 2009,87 (7) :549-555.
  • 5Novotna J, Herget J. Possible role of matrix metalloprotei- nases in reconstruction of peripheral pulmonary arteries in- duced by hypoxia [ J ]. Physiol Res, 2002, 51 ( 4 ) : 323- 334.
  • 6Toshner M, Voswinckel R, Southwood M, et al. Evidence of dysfunction of endothelial progenitors in pulmonary arte- rial hypertension[J]. Am J Respir Crit Care Med,2009, 180 (8) :780-787.
  • 7Kapakos G, Bouallegue A, Daou GB, et al. Modulatory role of nitric oxide/cGMP system in endothelin-l-induced signaling responses in vascular smooth muscle cells [ J ]. Curr Cardiol Rev,2010, 6(4) :247-254.
  • 8Hu H, Xin M, Belayev LL, et al. Autoinhibitory domain fragment of endothelial NOS enhances pulmonary artery va- sorelaxation by the NO-cGMP pathway [ J ]. Am J Physiol Lung Cell Mol Physio1,2004,286 (5) : L1066-L1074.
  • 9Murata T, Yamawaki H, Hod M, et al. Hypoxia impairs endothelium-dependent relaxation in organ cultured pulmo- nary artery[J]. Eur J Pharmacol,2001,421 ( 1 ) :45-53.
  • 10Braam B, Verhaar MC. Understanding eNOS for pharmaco- logical modulation of endothelial function: a translational view [ J ]. Curr Pharm Des, 2007,13 ( 17 ) : 1727 -1740.

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