卡托普利对放射性肾损伤中血管性血友病因子的影响
잡탁보리대방사성신손상중혈관성혈우병인자적영향
Effect of captopril on vWF in radiation renal injury
  • 万方数据
    中华放射医学与防护杂志 중화방사의학여방호잡지
    Chinese Journal of Radiological Medicine and Protection
    2013年 1期 32-37 ,共6页

    张银铃%曹永珍%张文学%耿凯%王克强%周琰%毛羽%魏健%李素芬

    장은령%조영진%장문학%경개%왕극강%주염%모우%위건%리소분

    放射性肾损伤%血管性血友病因子%胶原%卡托普利 放射性腎損傷%血管性血友病因子%膠原%卡託普利
    방사성신손상%혈관성혈우병인자%효원%잡탁보리
    Radiation renal injury%Von Willebrand factor%Collagen%Captopril
    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.
    목적 탐색잡탁보리대방사성신손상대서혈장화신소구중혈관성혈우병인자(vWF)적영향.방법 체중위280～300 g적웅성SD대서96지,채용수궤수자표법분위3조:건강대조조20지、단순조사조38지화잡탁보리+조사조38지.기중후량조대서쌍신접수5 MeV전자선일차성국부조사,제량위12 Gy.조사전24 h,잡탁보리+조사조대서개시접수농도위0.38 ～0.50 mg/ml적잡탁보리처리.조후48 h,1、2、4、8、16、24주,단순조사조화잡탁보리+조사조적대서피류취뇨화혈양본,기중제조사후2주외,기여시간점균취신장(매차매조6지).조사후48 h,4화24주,건강대조조대서피류취뇨、혈화신장양본(매차매조6지).용면역조직화학염색법검측신소구중vWF적개변,고미산-천랑성홍염색관찰신소구중효원적침적,매련면역흡부시험(ELISA)법검측대서혈장중광억소C화vWF적수평.검측뇨단백화뇨기항,계산뇨단백청제솔,HE염색방법검측대서신장조직적병리변화.결과 단순조사조조사후16화24주,신소구중vWF축점증가(t=3.53～6.95,5.71～12.66,P＜0.05)；조사후8、16화24주,신소구중적효원침적축점증가(t=3.03 ～5.13,3.48～4.68,4.68～9.03,P＜0.05),차vWF화효원침적지간유명현적정상관(r=0.819,P＜0.05).조사후2、4화16주,혈장vWF출현증가(t=3.93 ～ 5.03,4.04～5.15,3.48～ 4.58,P＜0.05)；조사후24주,혈장광억소C(t=5.10～6.17,P＜0.05)화뇨단백청제솔(t=14.59 ～16.34,P ＜0.05)개시증가,이차시신조직병리현시신장출현료경도적신소구계막적증생.재잡탁보리+조사조중,조사후2주,잡탁보리미명현지강저혈장vWF,단재기여시간점중,잡탁보리균명현지강저료신소구중적vWF(F=15.60,t=9.82,P＜0.05)、신소구중적효원침적(F=10.24,16.08,t=8.63,P＜0.05)、혈장vWF(t=3.77,P＜0.05;F=4.16,P＜0.05)、혈장광억소C(t =6.68,P＜0.05)화뇨단백청제솔(t=13.01,P＜0.05).차잡탁보리+조사조적대서신장미출현명현적병리변화.결론 잡탁보리능구강저방사성신손상대서혈장화신소구중적vWF,병유효지보호료신장.
    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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