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The pathogenesis of dysplastic kidney in a urinary tract obstruction in fetal lambs

胎羔尿路梗阻中肾脏发育不良的发病机制

基本信息

批准号：
11671777
负责人：
KITAGAWA Hiroaki
金额：
$ 1.28万
依托单位：
St. Marianna University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

Hypothesis : The type of renal dysplasia resulting from obstructive uropathy depends on the completeness of the obstruction and its timing with respect to the stage of glomerulogenesis at the time of the obstruction. We created a successful obstructive uropathy model in the fetal lamb to demonstrate the differing pathogenesis of renal dysplasia.Methods : Fetal lambs at 50, 60 and 90 days gestation were operated on. Male lambs underwent urethral and urachal ligation and female lambs had their urethra and urachus ligated transabdominally and created a similar to posterior urethral valve model (PUV). Some of the female lambs, unilateral ureteric ligation and created a vesico ureteric junction stenosis model (VUJ). They were returned to the uterus after the fetal surgery and delivered by cesarean section at 145 days (term).Results : Of 12 lambs operated on at 50 days gestation, 4 survived. Of 26 lambs operated on at 60 days, 21 survived. We identified 3 types of dysplastic kidneys. Type A : Fibrotic kidneys (2.2 gm) with no cysts and interstitial fibrosis. There were reduced numbers of proximal tubules but distal tubules and collecting ducts persisted. (50-day obstruction). Type B : Sponge-like kidneys (37 g) These had large cysts with minimal interstitial fibrosis. (87 % of 60 day uretheral and urachal ligation model n=12) Type C : Small kidneys (4.8 g) with no large cysts (60 day Ureteric ligation model n=7). Of 10 lambs operated at 90 days gestation had hydronephrosis without dysplastic kidney.Conclusion : All had dysplastic changes operated at 50 and 60 days gestation but most of the 60-day lambs with urethral and urachal ligation had enlarged kidneys with phenotypic features reminiscent of adult type polycystic kidney disease.

假设：梗阻性尿路病引起的肾发育不良的类型取决于梗阻的完整性及其与梗阻时肾小球形成阶段的关系。方法：对妊娠50、60和90 d的胎羊进行手术，雄羊经腹行尿道脐尿管结扎，雌羊经腹行尿道脐尿管结扎，建立类似后尿道瓣膜（PUV）的模型。部分雌性羔羊，单侧输尿管结扎，建立膀胱输尿管连接部狭窄模型（VUJ）。结果：12只妊娠50 d的羔羊中，4只存活，其余12只均在妊娠50 d时行剖宫产术。在60天时手术的26只羔羊中，21只存活。我们确定了3种类型的发育不良的肾脏。A型：纤维化肾脏（2.2 gm），无囊肿和间质纤维化。近端小管数量减少，但远端小管和集合管持续存在。（50天阻塞）。B型：海绵状肾（37 g），囊肿较大，间质纤维化轻微。(87 60天输尿管和脐尿管结扎模型的% n=12）C型：小肾脏（4.8 g），无大囊肿（60天输尿管结扎模型n=7）。10只羔羊在妊娠90天手术有肾积水，没有发育不良kidney.Conclusion：所有的发育不良的变化，在妊娠50和60天的手术，但大多数60天的羔羊尿道和脐尿管结扎扩大肾脏的表型特征，让人联想到成人型多囊肾病。