可复性单侧输尿管部分梗阻动物模型的建立

目的探索建立一种较为理想的、可复性强的输尿管部分梗阻的动物模型。方法选用雄性Wistar大鼠48只,应用输尿管对侧腰大肌悬吊术建立输尿管部分梗阻模型,分别于6个不同时相即造模后1、2、4、6、8周（解除梗阻后4周）、10周（解除梗阻后4周）各取8只动物,同位素肾动态扫描检测造模后不同时相梗阻肾功能受损情况、梗阻解除后肾功能恢复情况,光镜下观察不同梗阻时段肾脏病理改变。结果造模后2周成模,成模率为97.9%。肾动态显像：与梗阻前比较,梗阻肾肾小球滤过率明显降低（P〈0.05）。梗阻后4周解除梗阻,肾功能明显恢复;6周解除梗阻,肾功能不能恢复至正常。结论输尿管对侧腰大肌悬吊术是较为理想的输尿管部分梗阻模型,该方法成模率高,梗阻具有可逆性。     

维甲酸抑制大鼠单侧输尿管梗阻模型肾间质纤维化

目的探讨维甲酸对大鼠单侧输尿管梗阻(UUO)模型肾间质纤维化的影响。方法建立大鼠UUO模型前2d治疗组和对照组分别每天给予10mg/kg全反式维甲酸或溶媒皮下注射。观察模型第3、7和12天肾小管损害百分比、肾间质纤维化程度、肾间质巨噬细胞数、肾间质α-平滑肌肌动蛋白(α-SMA)、胶原Ⅲ和单核细胞趋化蛋白-1(MCP-1)mRNA的表达。结果维甲酸显著减轻肾小管损害和肾间质纤维化(P<0.01)。治疗组肾间质巨噬细胞数和肾间质α-SMA表达显著低于对照组(P<0.01)。维甲酸显著抑制胶原Ⅲ和MCP-1mRNA表达(P<0.01)。结论维甲酸减少大鼠UUO模型肾间质巨噬细胞浸润、降低胶原Ⅲ和MCP-1mRNA表达、抑制α-SMA蛋白的表达,从而减轻肾间质纤维化。     

大豆异黄酮对单侧输尿管梗阻大鼠肾间质纤维化的影响

大豆异黄酮是近年来国内外研究较多的一种具有抗细胞增殖、抗癌与抗衰老作用的非营养成分,现有资料表明,异黄酮还有抗炎、抗氧化的作用犤1犦,可以抑制单核/巨噬细胞的活化和迁移以及抑制细胞间黏附分子(ICAM-1)的表达犤2犦。本实验以大鼠单侧输尿管梗阻模型(UUO)为研究对象,研究异黄酮对梗阻肾病理改变、ICAM-1表达及巨噬细胞浸润的影响,初步探讨异黄酮对肾间质纤维化(RIF)的抑制作用及其机制。一、材料与方法1.动物模型:雄性Wistar大鼠,6周龄,体重180～200g,随机分为假手术组(S)18只、对照组(C)30只和异黄酮组(G)42只。大鼠UUO模…     

大鼠输尿管部分梗阻后平滑肌形态及功能改变

目的 探讨单侧输尿管部分梗阻后输尿管平滑肌超微结构、收缩功能和自律性的改变.方法 Wistar大鼠80只.随机分4组:8周实验组、8周对照组、16周实验组、16周对照组.每组20只.实验组大鼠左侧输尿管上1/2段腰大肌包埋造成单侧输尿管部分梗阻的动物模型,对照组仅分离左侧输尿管.成模后于不同实验点分离大鼠输尿管进行离体肌条实验,测定肌条的收缩幅度和频率的改变,并通过透射电镜观察梗阻后平滑肌超微结构的变化.结果 8周实验组输尿管收缩力和收缩频率分别为(0.62±0.38)g、(18.52±6.70)次/min,8周对照组分别为(0.38±0.36)g、(14.80±4.98)次/min,2组比较差异均有统计学意义(P＜0.05).16 周实验组输尿管收缩力和收缩频率分别为(0.15±0.10)g、(12.84±3.32)次/min,16周对照组分别为(0.41±0.38)g、(16.48±3.44)次/min.2组间比较差异均有统计学意义(P＜0.05).8周实验组均高于16周实验组(P＜0.05),8周对照组与16周对照组比较差异无统计学意义(P＞0.05).透射电镜观察到8周实验组平滑肌细胞胞质中线粒体数增多,而16周实验组平滑肌细胞胞质中线粒体数目减少、线粒体肿胀和空泡化、细胞间质中可见大量胶原纤维增生.结论 输尿管梗阻8周的大鼠输尿管肌条自律性和收缩力增加,输尿管平滑肌细胞胞质中线粒体增多,可能是机体代偿所致.输尿管梗阻16周后输尿管平滑肌自律性和收缩力均降低.平滑肌细胞胞质中线粒体数目减少,线粒体肿胀和空泡化,细胞间质中有大量胶原纤维增生,呈失代偿表现.     

依普利酮对大鼠单侧输尿管梗阻模型肾间质纤维化的影响

目的：研究依普利酮对大鼠单侧输尿管梗阻（UUO）模型肾间质纤维化的影响,探讨依普利酮的抗肾间质纤维化作用机制。方法：42只雄性Wistar大鼠随机分成假手术（SO）组、UUO组和UUO＋依普利酮治疗组（T-UUO组,依普利酮100mg.kg-1.d-1）。于术后7d、14d分别处死各组7只大鼠。免疫组织化学法测定α-平滑肌肌动蛋白（α-smoothmuscle actin,α-SMA）、单核细胞趋化蛋白-1（monocyte chemoattractant protein-1,MCP-1）、单核细胞/巨噬细胞-1（monocytes/macrophages-1,ED-1）,及增殖细胞核抗原（proliferative cell nuclear antigen,PCNA）的表达。结果：UUO组肾间质α-SMA、MCP-1、ED-1、PCNA的表达较SO组增加（P〈0.05）;在术后各时间点,使用依普利酮治疗的T-UUO组大鼠肾间质α-SMA、MCP-1、ED-1、PCNA的表达较UUO组显著减少（P〈0.05）,但仍高于SO组（P〈0.05）。结论：依普利酮可通过降低α-SMA和MCP-1表达、抑制单核/巨噬细胞浸润和和系膜细胞增生,减轻肾间质纤维化。     

单侧输尿管梗阻大鼠肾间质纤维化的发生机制

目的 探讨单侧输尿管梗阻后肾间质纤维化的形成机制.方法 采用单侧输尿管梗阻(uniliteral ureteral obstruction UUO)致肾间质纤维化大鼠模型,将54只大鼠随机分假手术组、梗阻组.术后7天、14天、21天观察肾组织病理改变,并应用免疫组织化学方法检测肾间质核转录因子-κB(Nuclear factor-κB NF-κB)、纤溶酶原激活物抑制剂-1(plasminogen activator inhibitor-1 PAI-1)的表达.结果 随着梗阻时间延长,梗阻组肾间质PAI-1和NF-κB的表达增加,假手术组无明显变化,两组相比有显著差异(p＜0.01).结论 单侧输尿管梗阻肾间质NF-κB、PAI-1的过度表达,是形成间质纤维化的重要原因之一.     

99mTc-DTPA肾动态显像检测肾小球滤过率的临床应用评价

目的 以^99mTc-DTPA血浆清除率为标准，评价^99mTc-DTPA肾动态显像检查在检测肾小球滤过率(GFR)中的应用价值。方法 选择慢性肾脏病患者197例，年龄均>18岁，诊断均符合美国NKF-K/DOQI关于慢性肾脏病定义。排除肾功能急性恶化因素、水肿、肢体缺如、心功能不全。记录身高、体重。肘静脉“弹丸”式注射^99mTc-DTPA 111 MBq后即刻行肾动态图像采集120 帧，计算双肾GFR，即Gates法，同时于注射后2、4 h各抽血4 ml，分离血浆1 ml，测量其放射性计数，计算99mTc-DTPA的血浆清除率(双血浆法)，所测数值均用体表面积标准化。按双血浆法所测得的GFR值将患者分成3组:A组 77例，GFR < 30 ml·min^-1·(1.73 m²)^-1；B组 74例， 30 ml·min^-1·(1.73 m²)^-1≤GFR < 90 ml·min^-1·(1.73 m²)^-1；C组 46例，GFR≥90 ml·min^-1·(1.73 m²)^-1。分别行肾动态显像法与双血浆法所测值之间的相关分析。 结果 肾动态显像法及双血浆法所测3组GFR[单位:ml·min^-1·(1.73 m²)^-1]分别为:A组 (27.08±12.14) 比 (17.68±5.66)；B组 (63.18±23.59) 比 (51.95±16.81)； C组 (107.28±27.36) 比 (117.96±24.17)。2者间的相关系数分别为rA=0.286(P=0.012)；rB=0.804(P < 0.01)；rC=0.473(P < 0.01)。结论 99mTc-DTPA肾动态显像检查适用于轻、中度肾功能不全患者GFR的评估，但在重度肾功能不全患者中，其测量结果的准确性有待进一步提高。     

肝细胞生长因子在单侧输尿管梗阻大鼠肾脏中的表达及其意义

目的　检测肝细胞生长因子 (HGF)在单侧输尿管梗阻 (UUO)大鼠肾脏中的表达并探讨其与小管细胞增殖与凋亡的关系。方法　免疫组织化学和脱氧核苷酸末端转移酶介导的核苷酸缺口末端标记 (TUNEL)法分别检测了第 0、3、6、9、1 2天UUO大鼠肾脏小管间质α 平滑肌肌动蛋白 (α SMA)、转化生长因子 β1 (TGF β1 )、HGF的表达以及小管细胞增殖性细胞核抗原 (PCNA)的表达和细胞凋亡的情况。噻唑蓝 (MTT)法检测重组HGF(rHGF)对培养的小管上皮细胞促增殖作用。结果　随着梗阻时间的延长 ,UUO大鼠肾脏α SMA、TGF β1蛋白的表达逐渐增多 ,HGF与PCNA蛋白的表达在第 6天达到高峰 ,随后逐渐下降 ,且它们之间呈正相关 (r =0 .870 5 ,P <0 .0 1 ) ,而细胞凋亡数随着时间的延长也逐渐增多。rHGF可促进体外培养的小管上皮细胞增殖。结论　HGF具有促进小管上皮细胞增殖的作用 ,同时它可能具有抗凋亡的作用     

抗纤灵冲剂对单侧输尿管梗阻大鼠肾组织氧化应激反应的影响

目的：研究抗纤灵冲剂对单侧输尿管梗阻（UUO）大鼠肾组织氧化应激的影响。方法：SD雄性大鼠120只,随机分为正常组、假手术组、模型组、抗纤灵组和科素亚组,各组分别观察28d。于造模后每周各组随机选取6只检测肾组织匀浆超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽（GSH）。结果：与正常组、假手术比较,模型组肾组织SOD、GSH明显降低（P〈0.01）,MDA明显升高（P〈0.01）。在UUO模型中,SOD、GSH、逐渐下降,MDA逐渐升高。抗纤灵组与模型组比较,肾组织SOD、GSH明显升高（P〈0.01）,MDA明显下降（P〈0.01）。结论：在肾间质纤维化的起始和发展过程中,都有氧化应激的参与。抗纤灵冲剂能有效缓解在大鼠UUO模型中肾组织氧化应激的反应,进而可能延缓肾间质纤维化的进程。     

和解聚散方对单侧输尿管梗阻大鼠肾间质纤维化的防治作用

目的：研究和解聚散方对单侧输尿管梗阻（unilateral ureteral obstruction,UUO）大鼠肾间质纤维化的防治作用。方法：采用UUO建立大鼠肾间质纤维化模型,随机分为模型组、贝那普利组和和解聚散方组,另设假手术组;术后7d、14d、21d分批取材,检测血清肌酐、尿素氮,采用HE和Masson染色检测肾脏病理、免疫组化法检测肾组织TGF-β1的表达。结果：与模型组相比,和解聚散方组血清尿素氮、血清肌酐水平均降低（P〈0.05）,肾小管损害百分比和肾间质损害分值较低（P〈0.05）,肾组织TGF-β1表达减少（P〈0.05）。结论：和解聚散方可以降低尿素氮、血清肌酐水平,减轻大鼠肾间质纤维化的程度,下调UUO大鼠肾组织TGF-β1的表达,验证了和解聚散法的正确性。     

Urinary PGE2 in rats with chronic partial unilateral ureteral obstruction

Urinary prostaglandin E2 (PGE2) was measured in Munich-Wistar rats with surgically created chronic partial unilateral ureteral obstruction (UUO). Mean values of bladder urine PGE2 were higher in sham than in UUO (24.5 +/- 14.4 vs 12.9 +/- 8.2 ng/mg creatinine, respectively, P less than 0.05). Following diuresis, both ureters were cannulated and urine was collected. PGE2 excretion was increased in sham (66.5 +/- 34.4 and 70.1 +/- 44.5 ng/mg creatinine, left and right, respectively). But in UUO, the obstructed kidney excreted less PGE2 than the contralateral kidney (32.1 +/- 6.0 vs 62.3 +/- 40.4 ng/mg creatinine, obstructed vs contralateral, respectively, P = 0.08). PGE2 synthesis was then determined in separated renal medullary and cortical slices. Renal medullary slices from kidneys with severe obstruction synthesized less PGE2 than the contralateral unobstructed side (3.30 +/- 1.22 vs 10.52 +/- 3.23 ng/mg wet wt-30 min, respectively, P less than 0.05) and failed to respond to arachidonic acid stimulation with any significant increase in PGE2 synthesis (3.30 +/- 1.22 vs 4.47 +/- 1.04 ng/mg wet wt-30 min, baseline vs stimulated). In contrast, contralateral unobstructed kidney slices responded with a significant increase in PGE2 synthesis (10.52 +/- 3.23 vs 21.10 +/- 2.50 ng/mg wet wt-30 min, baseline vs stimulated, P less than 0.05). We conclude that chronic partial UUO in the Munich-Wistar rats resulted in significantly less PGE2 elaboration.     

High urinary flow accelerates renal injury in young rats with partial unilateral ureteral obstruction

PURPOSE: We studied the effect of dietary manipulation and high urine flow on neonatal partial ureteral obstruction in a weanling rat preparation. MATERIALS AND METHODS: A total of 40, 3-week old Sprague-Dawley rats underwent unilateral ureteral obstruction by burial of the right ureter in the psoas muscle and 13 underwent sham operation. Low, high and normal salt, and high sucrose diets were administered for 2 months. The glomerular filtration rate of each kidney was measured by iothalamate clearance. Intrapelvic pressure and renal blood flow were measured before and after acute volume loading. RESULTS: Fluid intake and urine output were 8 to 10-fold greater in animals on high salt and high sucrose diets compared to those in rats on normal and low salt diets. Hydronephrosis was observed only in rats with partial obstruction and high urine flow. No difference in renal weight was noted. Relative glomerular filtration rate of the partially obstructed kidney was maintained when urine flow was normal but decreased significantly with high urine flow. Total glomerular filtration rate also decreased with high urine flow. Intrapelvic pressure was elevated significantly at baseline in partially obstructed kidneys with high urine flow. All kidneys with partial obstruction had significantly increased intrapelvic pressure with volume loading. Renal blood flow was not significantly decreased in rats with high urine flow. CONCLUSIONS: Chronic high urine flow causes loss of renal function in partially obstructed weanling rat kidneys. Research should be done to determine whether human infants with hydronephrosis and partial ureteral obstruction would benefit from the prevention of increased fluid and salt intake.     

婴儿梗阻性黄疸99mTc-EHIDA肝胆显像诊断价值和治疗探讨

目的 探讨SPECT(99mTc-EHIDA)肝胆肠道动态显像检查对婴儿梗阻性黄疸诊断及鉴别诊断的价值,并对婴儿梗阻性黄疸临床治疗方法 进行研究.方法 应用SPECT核素对24例已诊断为梗阻性黄疸的患儿进行肝胆肠道延时动态显像检查,明确临床诊断,鉴别梗阻部位和性质,并经手术及临床治疗证实,同时采取相应不同的治疗.结果 8例肝胆、肠道延时核素显像为胆汁淤滞型黄疸,其中5例因黄疸加重行经套管针胆囊内置管加压冲洗治愈,3例药物治愈.16例为先天性胆道闭锁(肝外型10例、肝内型6例)延时核素检查有肝脏显像,胆囊、肠道不显像.16例先天性胆道闭锁患儿中14例(肝外型10例、肝内型4例)行Kasai手术,术后均有胆汁排出,3例肝外型因胆瘘再次手术均病死,4例肝内型术后病死,手术后存活7例(50%).另外2例肝内型未及手术死于肝衰竭.本组患儿全部行SPECT核素检查,灵敏度为100%、特异度为66.7%、准确性为100%.结论 SPECT(99mTc-EHIDA)肝胆肠道动态显像可鉴别梗阻性黄疸的性质和部位,是安全有效的检查方法 ,有很高的诊断价值.先天性胆道闭锁患儿在适当药物治疗基础上尽早手术,术后亦应相应药物治疗.年龄小于60 d的胆汁淤滞性黄疸患儿先应以相应药物治疗2周,如胆红素升高则手术治疗.     

Pressure-flow relationship in partial obstruction of ureter in pigs

In 10 female pigs, the proximal part of the left ureter was obstructed for 10 weeks by implantation of the ureter into the psoas muscle. After 9 weeks of obstruction, 6 systems showed delayed or impaired drainage at renographic examination. Renal function was slightly impaired in 1 case. At operation, 4 systems were macroscopically normal while the rest showed slight to moderate dilatation. The intrapelvic resting pressure was normal in 8 of 9 cases. At perfusion, all systems responded within the normal limits at 8 cm3/min while high-pressure responses were found in 4 units above 8 cm3/min. No correlation was found between the resting pressure and the pressure response and the degree of dilatation or impairment of renal function.     

梗阻性肾病大鼠肾组织periostin的表达及意义

目的 研究梗阻性肾病大鼠肾组织periostin表达的变化及其与肾间质纤维化的相关性.方法 18只SD雄性大鼠按随机数字法分成3组:假手术组、模型组和贝那普利组,每组6只.用单侧输尿管结扎法建立梗阻性肾病大鼠模型.RT-PCR检测各组大鼠肾组织periostin和转化生长因子(TGF) β1的mRNA表达;ELISA检测各组大鼠肾组织periostin、血管紧张素Ⅱ( AngⅡ)、TGF- β1的蛋白水平;HE及Masson染色观察肾间质变化;免疫组化检测肾组织Ⅰ型胶原蛋白.结果 与假手术组比较,模型组大鼠肾组织periostin、TGF-β1、AngⅡ蛋白表达显著升高(均P＜0.05).与模型组比较,贝那普利组上述蛋白表达显著降低,差异有统计学意义(均P＜0.05).与假手术组比较,模型组大鼠肾组织periostin和TGF- β1的mRNA表达显著上调,差异有统计学意义(均P＜0.05),而贝那普利组periostin和TGF- β1的mRNA表达则显著下调(均P＜0.05).肾组织periostin蛋白表达与AngⅡ、TGF-β1和Ⅰ型胶原的蛋白表达以及肾间质纤维化积分均呈正相关(r值分别为0.652、0.781、0.776和0.825,均P＜0.05).结论 梗阻性肾病大鼠肾组织periostin呈高表达,其可能参与了梗阻性肾病肾间质纤维化进程.     

Effect of NADPH oxidases inhibition on the development of interstitial fibrosis in unilateral ureter obstruction rats

ObjectiveTo clarify whether the NADPH oxidases (NOXs) family contributed to the reactive oxygen species (ROS) production and subsequent interstitial fibrosis in unilateral ureter obstruction (UUO) rats. MethodsMale Wistar rats were randomly divided into sham operation group (n＝8), sham operation + apocynin treatment group (n＝8), UUO operation group (n＝8) and UUO operation+apocynin treatment group (n＝8). Either vehicle or apocynin (100 mg/kg per day) were given by gavage for 7 days after surgery. Rats were sacrificed at 7th day. ELISA was used to detect the activity of superoxide dismutase (SOD) and catalase (CAT), and the level of 8-iso-prostaglandin F2alpha (8-iso- PGF2α) in renal tissue. Western blotting was used to detect the protein expressions of NADPH oxidase subunit NOX2 and NOX4, α- smooth muscle actin(α-SMA), collagen I (COL-I) and the level of ERK1/ 2 phosphorylation (p-ERK1/2). ResultsUUO rats with vehicle displayed increased oxidative stress, as measured by renal tissue 8-iso-PGF2α, accompanied with increased renal expression of NADPH oxidases (NOX2, 1.5-fold and NOX4, 1.7-fold, respectively), compared with sham-operated rats (P＜ 0.05). Furthermore, vehicle treated UUO rats showed increased renal COL - I and α - SMA levels, compared with sham-operated rats (P＜0.05). ERK1/2 was also activated as detected by p-ERK1/2 expression in UUO rats with vehicle (P＜0.05). Apocynin treatment significantly decreased renal tissue 8-iso-PGF2α level and expressions of NOX2 (-28.7%) and NOX4 (-31.0%) in UUO rats, respectively, compared with vehicle treated rats (P＜0.05). And significant decrease of COL-I (-26.4%) and α-SMA expression (-80.0%) were also observed (P＜0.05). The activation of ERK1/2 in UUO rats was greatly inhibited by apocynin treatment (P＜0.01). Despite the pronounced dysregulation of pro – oxidative NOXs family, no compensatory increase of antioxidative enzyme activities occurred. ConclusionThe NOXs family contributes largely to the production of ROS and subsequent interstitial fibrosis after ureter ligation, and inhibition of the NOXs family may be a choice for preventing interstitial fibrosis.     

Obstructive anuria: unilateral cutaneous ureterostomy with remission of contralateral ureter obstruction

We experienced 1 case of obstructive anuria. This patient had received radiotherapy for uterine cancer. We performed unilateral cutaneous ureterostomy. Excretion of urine from the contralateral kidney occurred from the 17th postoperative day indicating improvement in renal functions. The possible mechanism for improvement of functions of the contralateral kidney is considered to be release of unilateral obstruction resulting in improvement in edema of tissues around kidney and ureter and remission of intravesical ureter obstruction caused by inflammation as a sequela of radiotherapy through improvement in inflammation.     

Acute unilateral obstruction of ureter. Disparity in divided renal function calculated from 131I-hippuran and 99mTc-DTPA renography

Fifteen patients with acute unilateral obstruction of ureter and 30 control patients were studied with simultaneous 131I-Hippuran and 99mTc-DTPA gamma camera renography. In severe outflow obstruction the relative function of the obstructed kidney was higher when calculated with Hippuran than with DTPA. No difference was found in the control subjects. This means that the glomerular filtration rate of an obstructed kidney may be relatively more reduced than the renal blood flow. Therefore, measurement of the single kidney fraction of total glomerular filtration rate has to be calculated with a glomerular filtered tracer, e.g., 99mTc-DTPA.