慢性间歇低氧大鼠模型中血管内皮生长因子对心、肺、肾血管的影响

目的建立类似阻塞型睡眠呼吸暂停低通气综合征(OSAHS)的慢性间歇低氧(chronicintermittenthypoxia,CIH)大鼠模型,观察CIH过程中血管内皮生长因子(VEGF)表达及其对血管的影响。方法16只健康雄性SD大鼠按随机数字表法分为2组:空白对照组(UC)8只,间歇低氧组(IH)8只。UC组大鼠不予任何处理。IH组大鼠每天9∶00～17∶00进行间歇低氧处理,持续28天。2组大鼠用HE染色观察心、肺、肾血管的病理改变,心肌毛细血管密度(capillarydensity,CD),肺、肾组织中小动脉血管壁厚度与外径之比(WT%);免疫组织化学法观察心、肺、肾的VEGF表达。结果(1)HE法:UC组大鼠心肌组织结构正常,IH组心肌灶性变性,心肌细胞肿胀,间质中有炎性细胞浸润。与UC组比较,IH组大鼠左室心内膜下CD增加6.5%(P<0.05),右室心内膜下CD无明显变化。IH组大鼠肺小动脉WT%较UC组增加90.5(P<0.05);IH组大鼠肾小动脉WT%较UC组增加87.5%(P<0.05)。(2)免疫组织化学法:IH组大鼠心肌VEGF表达强阳性,与UC组比较左、右心室肌中VEGF水平分别增加38.6%和87.0%(P<0.05),CD与心肌VEGF水平呈正相关(r=0.821,P<0.01)。与UC组比较,IH组大鼠肺小动脉VEGF表达水平增加85.6%,(P<0.05);肺小动脉的WT%和肺VEGF表达水平呈正相关(r=0.928,P<0.01)。IH组大鼠肾小动脉、肾间质及肾小球VEGF表达呈阳性,与UC组比较表达水平增加36.0%(P<0.05),肾小动脉WT%和肾VEGF表达水平呈正相关(r=0.978,P<0.01)。结论CIH大鼠心肌毛细血管增生,肺、肾小动脉管壁增厚,管腔狭窄,与低氧促使VEGF表达增加有关。

The effect of VEGF on the vessels of heart,lung and kidney in chronic intermittent hypoxia rats

Objective To set up the rat model of chronic intermittent hypoxia (CIH) which was similar to OSAHS,and to investigate the expression of VEGF and its effect on vessels during the development of CIH.Methods 16 male SD rats were randomly divided into two groups.Unhandled control (UC) group (n=8) and intermittent hypoxia (IH) group (n=8).The rats in UC group were not treated at all,however,the rats in IH group were treated by intermittent hypoxia for 28 days. The pathological changes of the vessels of heart,lung and kidney (HE staining),myocardial capillary density and the ratio between the thickness of vessel wall and external diameter (WT%) were observed.The expression of VEGF in tissues of heart,lung and kidney were observed by immunohistochemistry staining.Results (1) HE method:the changes of vessel in heart ,lung and kidney in UC group were not found,while the rat in IH group were found for myocardial cell swelling and inflammatory cell infiltration. The capillary density in the subendocardial myocardium of the left ventricle in IH rats increased by 6.5%,as compared with that of UC group (P<0.05),no changes were found in the right ventricle.The WT% of lung small artery in IH group increased by 90.5%, as compared with that of UC group (P<0.05);The WT% of kidney small artery in IH group increased by 87.5%, as compared with that of UC group (P<0.05).(2)Immunohistochemistry method:the expression of VEGF in myo- cardiumof IHrats wasintensive positive ,the expression of VEGFlevelsinleft andright ventricleincreased by38 .6 %and 87 .0 %respectively,as compared withthat of UCgroup (P<0 .05) .There was a positive correlation betweencapillary density andthe expression of VEGFin myocardium(r=0 .821 ,P<0 .01) .The levels of VEGFin lungarteries in IHratsincreased by 85 .6 %,as compared withthat of UCgroup (P<0 .05) .There was a positive corre-lation between WT%of lung arteries andlung VEGFexpression (r=0 .928 ,P<0 .01) .Thelevels of VEGFinre-nal in IHratsincreased by 36 .0 %,as compared withthat of UCgroup (P<0 .05) .There was a positive correlationbetween WT%of renal arteries and kidney VEGFexpression (r=0 .978 ,P<0 .01) .Conclusion The myocardialcapillary proliferation,the wall of lung and kidney arteries thickening andlumen stenosis caused by CIHis closelyre-lated withthe increase of VEGFexpression caused by hypoxia .