张银铃,曹永珍,张文学,耿凯,王克强,周琰,毛羽,魏健,李素芬.卡托普利对放射性肾损伤中血管性血友病因子的影响[J].中华放射医学与防护杂志,2013,33(1):32-37
卡托普利对放射性肾损伤中血管性血友病因子的影响
Effect of captopril on vWF in radiation renal injury
投稿时间:2012-07-28  
DOI:10.3760/cma.j.issn.0254-5098.2013.01.008
中文关键词:  放射性肾损伤  血管性血友病因子  胶原  卡托普利
英文关键词:Radiation renal injury  Von Willebrand factor  Collagen  Captopril
基金项目:卫生部卫生标准研究课题(2010/9/03)
作者单位E-mail
张银铃 300052 天津医科大学总医院放疗科  
曹永珍 300052 天津医科大学总医院放疗科 cyz1956@hotmail.com 
张文学 300052 天津医科大学总医院放疗科  
耿凯 300052 天津医科大学总医院放疗科  
王克强 300052 天津医科大学总医院放疗科  
周琰 300052 天津医科大学总医院放疗科  
毛羽 300052 天津医科大学总医院放疗科  
魏健 天津大港油田总医院  
李素芬 天津大港油田总医院  
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中文摘要:
      目的 探索卡托普利对放射性肾损伤大鼠血浆和肾小球中血管性血友病因子(vWF)的影响。方法 体重为280~300 g的雄性SD大鼠96只,采用随机数字表法分为3组:健康对照组20只、单纯照射组38只和卡托普利+照射组38只。其中后两组大鼠双肾接受5 MeV电子线一次性局部照射,剂量为12 Gy。照射前24 h,卡托普利+照射组大鼠开始接受浓度为0.38~0.50 mg/ml的卡托普利处理。照后48 h,1、2、4、8、16、24周,单纯照射组和卡托普利+照射组的大鼠被留取尿和血样本,其中除照射后2周外,其余时间点均取肾脏(每次每组6只)。照射后48 h,4和24周,健康对照组大鼠被留取尿、血和肾脏样本(每次每组6只)。用免疫组织化学染色法检测肾小球中vWF的改变,苦味酸-天狼猩红染色观察肾小球中胶原的沉积,酶联免疫吸附试验(ELISA)法检测大鼠血浆中胱抑素C和vWF的水平。检测尿蛋白和尿肌酐,计算尿蛋白清除率,HE染色方法检测大鼠肾脏组织的病理变化。结果 单纯照射组照射后16和24周,肾小球中vWF逐渐增加(t=3.53~6.95, 5.71~12.66, P<0.05);照射后8、16和24周,肾小球中的胶原沉积逐渐增加(t=3.03~5.13, 3.48~4.68, 4.68~9.03, P<0.05),且vWF和胶原沉积之间有明显的正相关(r=0.819,P<0.05)。照射后2、4和16周,血浆vWF出现增加(t=3.93~5.03,4.04~5.15,3.48~4.58,P<0.05);照射后24周,血浆胱抑素C(t=5.10~6.17,P<0.05)和尿蛋白清除率(t=14.59~16.34,P<0.05)开始增加,而此时肾组织病理显示肾脏出现了轻度的肾小球系膜的增生。在卡托普利+照射组中,照射后2周,卡托普利未明显地降低血浆vWF,但在其余时间点中,卡托普利均明显地降低了肾小球中的vWF(F=15.60, t=9.82, P<0.05)、肾小球中的胶原沉积(F=10.24,16.08,t=8.63,P<0.05)、血浆vWF(t=3.77, P<0.05;F=4.16,P<0.05)、血浆胱抑素C(t=6.68,P<0.05)和尿蛋白清除率(t=13.01,P<0.05)。且卡托普利+照射组的大鼠肾脏未出现明显的病理变化。结论 卡托普利能够降低放射性肾损伤大鼠血浆和肾小球中的vWF,并有效地保护了肾脏。
英文摘要:
      Objective To explore the effect of captopril on plasma and glomerular vWF in radiation renal injury.Methods A total of 96 male SD rats weighing 280-300 g were randomly divided into three groups: control group(n=20), radiation alone group(n=38), captopril+radiation group(n=38). The latter two groups were subjected to a single-dose of 12 Gy 5 MeV electron rays to the kidneys. The captopril+radiation group began to receive captopril at the concentration of 0.38-0.50 mg/ml at 24 h before irradiation. The blood and urine samples were collected in the radiation alone and captopril+radiation groups at 48 h, 1, 2, 4, 8, 16, 24 weeks after irradiation (six rats per time in each group). Except for the 2 weeks after irradiation, kidneys were removed in the two groups at other point in time(six rats per time in each group). The kidneys, blood and urine samples were collected in the control group at 48 h, 4, 24 weeks after irradiation (six rats per time in each group). The glomerular vWF was detected by immunohistochemistry, collagen deposition in glomeruli by Sirius Red F3B in saturated carbazotic acid stain and plasma vWF and cystatin C levels by ELISA. Roche biochemical automatic analyzer and roche specific reagent were used to examine urine protein and urine creatinine, and urine protein clearance by urine protein and urine creatinine were calculated. The renal morphological feature was observed under light microscope after HE staining.Results In radiation alone group, glomerulus vWF increased gradually at 16 and 24 weeks after irradiation(t=3.53-6.95, 5.71-12.66, P<0.05),collagen deposition in glomerular also gradually increased at 8, 16 and 24 weeks after irradiation(t=3.03-5.13, 3.48-4.68, 4.68-9.03, P<0.05), and there was an obvious positive correlation between collagen and vWF (r=0.819, P<0.05). There was an increase in plasma vWF at 2, 4 and 16 weeks after irradiation (t=3.93-5.03, 4.04-5.15,3.48-4.58,P<0.05), plasma cystatin-C (t=5.10-6.17,P<0.05) and urinary protein clearance(t=14.59-16.34, P<0.05) at 24 weeks after irradiation, and the pathological changes of kidney were mild mesangial proliferation at 24 weeks after irradiation. In captopril+radiation group, captopril failed to decrease plasma vWF at 2 weeks after irradiation (P>0.05). Except for that, captopril reduced glomerulus vWF(F=15.60, t=9.82, P<0.05),collagen deposition in glomerular (F=10.24,16.08,t=8.63,P<0.05), plasma vWF (t=3.77, P<0.05; F=4.16,P<0.05), plasma cystatin-C (t=6.68, P<0.05) and urinary protein clearance(t=13.01, P<0.05), and obvious renal pathological changes were not observed in captopril+radiation group.Conclusions Captopril can reduce plasma and the glomerulus vWF in radiation renal injury, and effectively protect the kidney.
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