新生鼠输尿管不全梗阻后肾盂压力和肾脏形态变化的观察

目的 了解新生鼠输尿管不全梗阻后肾盂压力和肾脏形态的变化。方法 65只新生鼠用腰大肌包埋不同长度的左侧输尿管，制成轻（n=31)、重（n=34)度输尿管不全梗阻。对照组仅进行剖腹探查。术后8周和24周分别用核磁共振检查肾脏形态变化，术后分别于24周和30周进行肾盂测压和组织学检查。结果 梗阻肾脏均有不同程度积水。严重梗阻组除积水较严重外，发现4例肾脏肾发育不全，其平均肾实质重量仅是对照组的35％。轻度梗阻组和对照组未见发育不良的肾脏。严重梗阻组的肾脏灌注压明显高于轻度梗阻组和正常对照组。结论 新生鼠输尿管不全梗阻后均产生明显肾积水。严重梗阻组可产生肾脏发育不良，可能与严重梗阻组肾盏灌注压明显增加有关。     

新生鼠输尿管梗阻对肾脏发育的影响

目的：研究新生鼠单侧输尿管梗阻（UUO）对肾脏发育的影响。为临床评价肾积水所致肾功能损害提供依据。方法：生后48h内对70只Wister新生鼠行单侧输尿管结扎或假手术。在术后的第1－28d切取肾脏，测其重量，取术后14d的肾脏分别行α－平滑肌（α－SM）肌动蛋白和转化生长因子－β1（TGF－β1）免疫组化免疫。结果：UUO侧肾脏重量增长明显受到抑制，而对侧出现代偿性增长。术后14d的切片观察到α－SM肌动蛋白在梗阻侧肾脏中仍持续存在，而在对侧及假手术组肾中已消失。TGF－β1在梗阻侧肾脏中表达增强。结论：新生鼠UUO明显影响了同侧肾脏发育，并使肾功能受到损害。     

Chronic partial ureteral obstruction in the neonatal guinea pig. I. Influence of uninephrectomy on growth and hemodynamics

Although obstructive nephropathy is a frequent cause of renal insufficiency in infancy, factors influencing adaptation to chronic partial ureteral obstruction (CPUO) are poorly understood. Guinea pigs were subjected to unilateral CPUO within the first 2 days of life (Group I) and microsphere studies were performed at 23 +/- 3 days of age. To also investigate the role of functional renal mass on growth and hemodynamics, contralateral nephrectomy was performed in Group II at the time of ureteral constriction. Compared to sham-operated controls (ureteral diameter = 1 mm) CPUO caused impaired somatic growth in both groups. Resulting hydroureteronephrosis was variable and most severe (ureteral diameter greater than 3 mm) in azotemic animals of Group II, which demonstrated reduced compensatory renal hypertrophy and poorest somatic growth. Mean arterial blood pressure was not affected by CPUO or uninephrectomy. Renal blood flow (RBF) was higher in Group II than Group I, and did not fall significantly with severity of CPUO in Group II, in which number of perfused glomeruli was similar to controls. In contrast, renal vascular resistance (RVR) increased by 172% in animals of Group I with severe CPUO, and was associated with 34% fewer perfused glomeruli than in the hypertrophied contralateral kidney. With increasing severity of CPUO, RBF tended to be distributed to outer cortical regions in the obstructed kidney of Group I, while the shift in RBF distribution was from outer to inner cortex in the remaining kidney of Group II. Filtration fraction fell as a result of CPUO in both groups, such that reduction in the glomerular filtration rate was due in large part to factors other than RBF.(ABSTRACT TRUNCATED AT 250 WORDS)     

胎儿期解除单侧输尿管不完全梗阻的实验研究

目的 探讨胎儿期解除单侧输尿管不完全梗阻的效果.方法 取22只健康孕羊在妊娠第75至85天采用宫内手术的方法 造成胎羊左侧输尿管不完全梗阻.然后分为二组,第一组12只继续妊娠,第二组10只三周后再次手术去除胎羊输尿管上的硅胶环和丝线以解除梗阻.对羔羊进行影像、病理学研究.结果第一组12只孕羊中有3只流产,有9只孕羊顺产羔羊;第二组10只孕羊中有2只流产,有8只孕羊顺产羔羊.第一组羔羊左肾均可见增大、积水和肾功能损害;第二组羔羊左肾大小、肾功能正常,左肾盂无扩张,但表面不平滑、肾实质较薄.组织学上,第二组羔羊左肾肾小球数目无减少,肾小管扩张也较第一组羔羊左肾轻.结论 胎儿期解除单侧输尿管不完全梗阻,可以及时阻止病程进展,使梗阻解除肾在形态和功能上都可得到较好的恢复.     

Chronic partial ureteral obstruction and the developing kidney

Although congenital urinary tract obstruction is a common disorder, its pathophysiology remains poorly understood and clinical practice is controversial. Animal models have been used to elucidate the mechanisms responsible for obstructive nephropathy, and the models reveal that renal growth and function are impaired in proportion to the severity and duration of obstruction. Ureteral obstruction in the neonatal rat or mouse leads to activation of the renin-angiotensin system, renal infiltration by macrophages, and tubular apoptosis. Nephrons are lost by glomerular sclerosis and the formation of atubular glomeruli, and progressive injury leads to tubular atrophy and interstitial fibrosis. Recovery following release of obstruction depends on the timing, severity, and duration of obstruction. Growth factors and cytokines are produced by the hydronephrotic kidney, including MCP-1 and TGF-beta1, which are excreted in urine and can serve as biomarkers of renal injury. Because MRI can be used to monitor renal morphology, blood flow, and filtration rate, its use might supplant current imaging modalities (ultrasonography and diuretic renography), which have significant drawbacks. Combined use of MRI and new urinary biomarkers should improve our understanding of human congenital obstructive nephropathy and should lead to new approaches to evaluation and management of this challenging group of patients.     

Chronic partial ureteral obstruction in the neonatal guinea pig. II. Pressure gradients affecting glomerular filtration rate

Neonatal guinea pigs with chronic partial ureteral obstruction (CPUO) and contralateral nephrectomy develop hydroureteronephrosis and reduced glomerular filtration rate (GFR) without significant reduction of renal blood flow. To investigate the role of pressure gradients in determination of GFR, micropuncture studies were performed in animals 23 +/- 3 days of age subjected to left ureteral constriction and right nephrectomy within the first 2 days of life and compared to uninephrectomized controls. Resulting ureteral dilatation was variable, with kidney weight and ureteral diameter being proportional to the rise in ureteral pressure (PU). In individual animals with severe CPUO (ureteral diameter greater than or equal to 3 mm), distal tubular transit time was either normal (31-90 s) or prolonged (greater than 120 s). Superficial single nephron GFR (SNGFR) was inversely correlated with PU. Glomerular capillary pressure and afferent arteriolar colloid oncotic pressure were not affected by CPUO while peritubular capillary, proximal and distal intratubular hydrostatic pressure increased as a function of PU. As a result, afferent effective filtration pressure (EFPA) was reduced in severe (10.0 +/- 1.1 mm Hg) compared to mild CPUO (13.4 +/- 0.5 mm Hg), but was not different from controls (11.3 +/- 0.9 mm Hg). For both control and CPUO groups, superficial SNGFR increased by 0.5 nl/min for each mm Hg increase in EFPA but for a given EFPA, SNGFR was 6 nl/min lower in guinea pigs with CPUO. These results indicate that higher EFPA in animals with mild compared to severe CPUO contributes to maintenance of higher SNGFR.(ABSTRACT TRUNCATED AT 250 WORDS)     

喹那普利对单侧输尿管结扎大鼠肾纤维化拮抗作用的研究

目的 研究喹那普利对梗阻性肾病肾间质纤维化的影响及其机制。方法 30只SD大鼠随机分为3组：假手术组（n＝6）、单侧输尿管结扎(UUO)组（n＝12）和喹那普利组（n＝12）。喹那普利组在UUO术前1 d予喹那普利10 mg·kg-1·d-1 灌胃,假手术组及UUO组予同等体积生理盐水灌胃。各组大鼠分别于术后14和28 d取梗阻侧肾组织。采用Masson染色及免疫组化方法观测各组大鼠的肾间质容量、肾组织α-平滑肌肌动蛋白（α-SMA）及转化生长因子-β1（TGF-β1）蛋白水平的变化。以原位杂交法检测各组大鼠肾组织TGF-β1 mRNA表达的变化。结果 与假手术组比较,UUO组大鼠肾小管明显萎缩塌陷或极度扩张,伴肾间质增生,输尿管梗阻后4周时上述病理改变尤为明显,肾间质容量明显升高(P<0.001)。免疫组化染色检测结果显示,UUO组α-SMA及TGF-β1蛋白水平均明显高于假手术组,且随梗阻时间的延长呈进行性升高(P<0.001)。原位杂交结果表明,UUO组TGF-β1 mRNA在肾小管间质中的表达显著高于假手术组(P<0.001)。喹那普利组肾间质容量、肾小管间质中TGF-β1 mRNA表达、TGF-β1蛋白和α-SMA水平均显著低于UUO组(P<0.05或<0.01)。结论 喹那普利可明显抑制肾组织分泌TGF-β1,可能的机制之一是减少其下游效应细胞-肌纤维母细胞的活化,从而减缓UUO大鼠肾纤维化进程。     

幼鼠双侧输尿管梗阻24 h后肾脏水通道蛋白1-4的变化

目的探讨4个月大白鼠双侧输尿管急性梗阻24h后肾脏水通道蛋白1-4的变化。方法14只大白鼠随机分为梗阻组（bilateral ureteral obstruction，BUO，n：7）及对照组（Sham，n=7），梗阻组行双侧输尿管结扎，对照组仅游离输尿管而不结扎，24h后收集动脉血和肾标本，在显微镜下将肾脏分离出内髓（IM）及外髓外带加肾皮质（OSOM＋C）后，分别行免疫杂交实验，检测水通道蛋白。（AQP1-4）的变化。结果BUO24h使血浆渗透压明显增高至（338±3．0）mOsm，原为（300±0．6）mIsm，P〈0．01，血钾显著上升至（5．4±0．2）mmol／L，原为（4．0±0．1）mmol／L，P〈0．01；血浆肌苷（372±5．3）μmol／L，原为（30±2．8）μmol／L，P〈0．01和尿素氮（40．7±1．4）mmol／L，原为（5．8±0．2）mmol／L，P〈0．01明显高于对照组，而血钠低于正常（138．9±0．3）mmol／L，原为（141．0±0．3）mmol／L，P〈0．01。免疫杂交结果发现近端小管上皮细胞AQP，明显降低，下降到对照组的46．6％（P〈0．01）；在肾脏集合管主细胞顶膜上，AQP2的表达明显下降，为对照组的68．1％（P〈0．01）；而基底膜上分布的AQR和AQP4也明显下调，分别为对照组的76．3％和73．2％（P〈0．01）。结论双侧输尿管梗阻24h显著影响肾脏AQP。在近端小管和AQP24。在集合管的表达，使其明显下调。该变化可能对梗阻后水分重吸收障碍并引发低渗性多尿的病理生理过程起重要作用。     

Refluxing ureteral reimplantation: A logical method for managing neonatal UVJ obstruction

ObjectiveAn obstructed megaureter can be managed using a number of techniques, with the primary goal being to minimize the potential for further injury to the affected kidney. Classically, these obstructed ureters have been treated using cutaneous ureterostomy. However, this technique has certain limitations including the potential for stenosis. We describe our experience with the refluxing ureteral reimplantation as a novel, yet technically simple, method for temporary internal diversion of the obstructed megaureter.MethodsTreatment consists of transecting the ureter proximal to the obstruction and performing an end-to-side anastomosis with the bladder in a freely refluxing fashion. Patients are placed on antibiotic suppression following surgery. Subsequent open definitive surgery is performed through the same incision site once the child is older than 1 year of age.ResultsSixteen patients identified with severe hydroureteronephrosis were found to have an obstructed megaureter(s) involving 19 ureteral moieties. Patients underwent internal diversion at an average age of 5 months. All patients demonstrated improved drainage of the affected kidney(s) following surgery. Three patients developed a febrile urinary tract infection. Definitive surgical treatment was undertaken in 18 of 19 ureters, and consisted of ureteral reimplantation with tapering or plication (13), ureteral reimplantation without tapering (3), and nephrectomy (2). One patient with multiple other congenital anomalies is not a candidate for further genitourinary reconstruction.ConclusionsRefluxing ureteral reimplantation is a safe and easy method of temporary internal urinary diversion. Simple in principle, the concept of creating a refluxing ureteral reimplantation is no different from that of incising an obstructing ureterocele. This technique allows time for the child to mature, while preserving renal function and awaiting definitive repair.     

苦参碱对单侧输尿管梗阻后肾间质纤维化调节作用研究

目的探讨苦参碱对梗阻性大鼠肾间质纤维化的影响。方法将54只大鼠中的36只行单输尿管结扎术(UUO),另18只行假手术。结扎后的大鼠分为模型组和苦参碱组各18只,术后第5、10及15天分别处死各组中的6只大鼠,用免疫组化法测定结缔组织生长因子(CTGF)、α-平滑肌肌动蛋白(α-SMA)、I型胶原(Col I)的表达情况;行HE和Masson染色,动态观察肾脏病理变化。结果苦参碱能显著减少肾组织CTGF的表达,减少处于增殖状态下的细胞数和肾小管间质区肌成纤维细胞(MyoF)的浸润,减轻Col I的沉积,并有效地改善肾脏的病理变化。结论苦参碱对梗阻性大鼠肾间质纤维化有抑制作用,其作用机制可能为下调CTGF的蛋白水平,从而减轻肾间质纤维化,提示苦参碱有潜在的延缓慢性肾功能衰竭进程的作用。     

Bilateral ureteral obstruction and renal failure due to a perforated appendix

Bilateral ureteral obstruction secondary to appendicitis is rare. We here report a case in which the obstruction caused anuria and renal failure.     

尿生物标记物对输尿管梗阻致肾脏早期损伤的临床意义

早期肾脏发育过程中的尿路梗阻影响肾脏形态发生及生长,严重的将导致肾功能不全.15％ ～20％的梗阻性肾病患儿需要早期手术以维持肾功能,而部分没有显著肾功能下降的患儿有自然消退的趋势,可以行保守治疗.目前的影像学检查对于输尿管梗阻存在不确定性和有创性,因此寻找能反映肾结构变化以及进行性肾功能下降的尿生物标记物显得尤为重要...     

肾间质纤维化大鼠纤维化相关基因的初步筛查

肾间质纤维化 (renalinterstitialfibrosis ,RIF)是各种肾脏病慢性进展的最终结果[1,2 ] 。其发生的分子机制目前尚未明了。为此 ,我们于 2 0 0 1年 7月～ 2 0 0 1年 12月运用中国科学院生物化学与细胞生物学研究所提供的含有 90 0 0条人类基因cDNA微矩阵表达芯片 (也称基因芯片 ) ,对单侧输尿管梗阻 (unilateralureteralobstruction ,UUO)大鼠RIF肾组织基因表达谱进行了研究 ,以期寻找RIF相关基因 ,报道如下。材料和方法1 动物分组和模型制备 :SD雄性大鼠 2 0只 ,随机分 2组 :模型组和对照组 (假手术组 )各 10只。模型制作参照文献 …     

双环醇对单侧输尿管梗阻大鼠肾间质纤维化的影响及其机制

目的 通过双环醇干预单侧输尿管梗阻(UUO)模型大鼠,动态观察核转录因子-κB(NF-κB)、细胞间黏附因子-1(ICAM-1)在梗阻侧肾间质中的表达,探讨双环醇延缓肾间质纤维化(RIF)的机制.方法 建立 UUO致肾间质纤维化大鼠模型,将81只大鼠随机分为假手术组、模型组、治疗组.治疗组于术后第1天开始给予双环醇200 mg/kg灌胃;假手术组和模型组给予等量生理盐水灌胃.在术后第7、14、21天每组各取9只处死,取动脉血分离血清测血肌酐和血尿素氮,观察大鼠肾功能变化.取梗阻侧肾组织行苏木精-伊红及Masson染色,观察肾脏病理学变化.用免疫组化方法检测肾组织NF-κB 、ICAM-1表达.结果 治疗组血清肌酐和尿素氮较模型组显著下降,差异有统计学意义(P ＜ 0.01).治疗组肾小管间质损伤评分和RIF相对面积均低于模型组(P均＜ 0.05).治疗组肾组织的NF-κB、ICAM-1蛋白表达显著低于模型组(P均＜ 0.05).结论 双环醇能够减轻UUO所致的肾间质损伤及RIF程度,其作用机制可能177(11):7485-7496.     

双环醇对单侧输尿管梗阻大鼠肾间质PAI-1 表达的影响

目的：探讨双环醇延缓肾间质纤维化的可能机制。方法：将 81 只Sprague-Dawley (SD)大鼠随机分为假手术组,模型组和治疗组 3 组。采用单侧输尿管梗阻（UUO）致肾间质纤维化大鼠模型,治疗组在制模后给予双环醇灌胃治疗。7、14、21 d取梗阻侧肾组织行苏木精-伊红及 Masson 染色,观察肾脏病理学变化。免疫组化法检测肾组织纤溶酶原激活物抑制-1（PAI-1） 的表达。RT-PCR 法检测肾组织 PAI-1 mRNA 的表达水平。结果：治疗组7 d、14 d、21 d肾间质纤维化的相对面积分别为 （9.6±0.6）%、（16.8±0.8）%、（33.6±1.6）%,较模型组［分别为（13.0±0.7）%、（25.8±1.5）%、（53.2±2.5）%］明显降低（均P<0.05);同时治疗组肾组织 PAI-1 蛋白表达及PAI-1 mRNA的表达均较模型组减少（均P<0.05)。结论：双环醇能够减轻 UUO 所致的肾间质损伤及纤维化程度,其作用机制可能是通过下调 PAI-1 的表达从而延缓肾间质纤维化的进程,发挥对肾脏的保护作用。     

Prohibitin在单侧输尿管梗阻大鼠肾间质纤维化中的表达和作用

目的探讨Prohibitin(PHB)在单侧输尿管梗阻(UUO)大鼠肾脏组织中的表达和作用。方法48只雄性6周龄Wistar大鼠随机分为假手术组和模型组,每组24只,模型组大鼠麻醉后,背侧切口行左侧输尿管结扎术,假手术组只探及肾包膜,造模后分别于第7、14、21、28天各处死6只大鼠,行肾脏病理检查并计算肾间质纤维化指数,采用实时荧光定量PCR和免疫组织化学方法检测肾脏组织中PHB与转化生长因子-β1(TGF-β1)mRNA和蛋白表达。结果与假手术组相比,模型组各时间点肾间质纤维化指数显著增高(P<0.01),梗阻时间越长纤维化指数越高;模型组各时间点PHB的mRNA和蛋白表达显著减少(P<0.01),梗阻时间越长,表达量越低;模型组各时间点TGF-β1的mRNA和蛋白的表达显著增高(P<0.01),梗阻时间越长,表达量越高。模型组PHB的蛋白表达与间质纤维化指数呈显著负相关(r=-0.825),TGF-β1的蛋白表达与间质纤维化指数呈显著正相关(r=0.995),PHB蛋白表达与TGF-β1蛋白表达呈显著负相关(r=-0.786)。结论UUO大鼠肾脏组织PHB表达显著降低,可能参与肾间质纤维化的发生发展。     

双环醇对单侧输尿管梗阻大鼠肾间质PAI-1表达的影响

目的探讨双环醇延缓肾间质纤维化的可能机制。方法将81只Sprague-Dawley(SD)大鼠随机分为假手术组,模型组和治疗组3组。采用单侧输尿管梗阻(UUO)致肾间质纤维化大鼠模型,治疗组在制模后给予双环醇灌胃治疗。7、14、21 d取梗阻侧肾组织行苏木精-伊红及Masson染色,观察肾脏病理学变化。免疫组化法检测肾组织纤溶酶原激活物抑制-1(PAI-1)的表达。RT-PCR法检测肾组织PAI-1 mRNA的表达水平。结果治疗组7 d、14 d、21 d肾间质纤维化的相对面积分别为(9.6±0.6)%、(16.8±0.8)%、(33.6±1.6)%,较模型组[分别为(13.0±0.7)%、(25.8±1.5)%、(53.2±2.5)%]明显降低(均P<0.05);同时治疗组肾组织PAI-1蛋白表达及PAI-1 mRNA的表达均较模型组减少(均P<0.05)。结论双环醇能够减轻UUO所致的肾间质损伤及纤维化程度,其作用机制可能是通过下调PAI-1的表达从而延缓肾间质纤维化的进程,发挥对肾脏的保护作用。     

双侧输尿管梗阻后大白鼠肾脏水通道蛋白2的变化

目的选择大白鼠模拟双侧输尿管梗阻模型,检测其肾脏水通道蛋白2(AQP2)的变化,以期从分子水平上阐明泌尿系梗阻解除后排尿量增多的病理生理改变。方法选取3个月雄性慕尼黑大白鼠(MunichWistarRats)12只,体重225g左右,随机分为实验组(n=6)及对照组(n=6),实验组行双侧输尿管梗阻24h后解除梗阻,对照组仅行输尿管游离而不结扎。每日观察体重、饮水量、食量、尿量变化,3d后取出肾标本,左肾全肾、右肾分离出内髓后行免疫杂交试验,检测水通道蛋白2(AQP2)的变化。结果解除输尿管梗阻后,实验组体重迅速下降(P<0.001),并排出大量低渗性尿液,渗透压明显低于对照组(P<0.05),术后每日排出尿量显著增高(P<0.001);血浆渗透压增高(312±4.71vs301±0.45mmol/L,P<0.05)。全肾及内髓检查,发现AQP2明显降低(P<0.01),而以集合管为主的内髓更为敏感。结论泌尿系梗阻影响肾脏对尿液的重吸收和浓缩功能,排出大量低渗尿液,同时体重明显下降,体内脱水严重;AQP2表达减少是肾脏集合管重吸收水分少、尿液浓缩功能差的主要原因。     

双环醇对单侧输尿管梗阻大鼠肾间质结缔组织生长因子、基质金属蛋白酶组织抑制物-1的影响

目的观察双环醇对单侧输尿管梗阻(UUO)大鼠肾间质结缔组织生长因子(CTGF)、基质金属蛋白酶组织抑制物-1(TIMP-1)介导的肾间质纤维化(RIF)的影响,探讨其可能的肾脏保护机制。方法采用UUO致RIF大鼠模型。将大鼠随机分为假手术组、模型组、治疗组。从造模当天起,治疗组给予双环醇200 mg/(kg.d)灌胃,假手术组和模型组给予等体积生理盐水灌胃。术后第7、14、21天各组随机处死9只大鼠,肉眼观察肾脏的大体结构改变;行苏木精-伊红和Masson染色观察肾间质的病理学改变,评定小管间质损伤及肾间质纤维化程度;用免疫组织化学方法检测CTGF和TIMP-1的表达部位及蛋白表达水平;应用逆转录-聚合酶链反应(RT-PCR)检测肾组织TIMP-1 mRNA的表达水平。结果假手术组大鼠肾脏大体及病理无明显异常,与假手术组比较,随着输尿管梗阻时限延长,模型组大鼠结扎侧肾脏明显肿大,肾间质损伤程度明显加重(P<0.01),肾组织内CTGF、TIMP-1及TIMP-1 mRNA的表达均显著上调(P<0.01)。治疗组大鼠上述变化均较模型组轻(P<0.01)。结论双环醇可能通过抑制TIMP-1、CTGF在UUO大鼠肾...