胎羊单侧输尿管不完全性梗阻解除前后肾脏组织足细胞表型转化及PAX2、VEGF的表达

Objective To investigate ultrastructure and molecular change of kidneys after correction of partial unilateral ureteral obstruction. Methods The 26 fetal lambs at 75-85 days of gestation were divided into 3 groups. Obstructed group: partial unilateral ureteral obstruction was achieved with intrauterine surgery in 12 fetal lambs. Decompressed group: partial unilateral ureteral obstruction in 10 fetal lambs first was released 3 weeks later by intrauterine surgery. Control group: a sham operation was performed. The kidneys of the lambs were removed after birth to study the transformation of podocytes as well as expression of paired-box 2 (PAX2) and vascular endothelial growth factor (VEGF). Results Overall, 21 fetal lambs survived: 9 from the obstructed group, 8 from the decompressed group, and 4 from the control group. Compared with the control kidneys, the obstructed kidneys showed cysts of various sizes in the cortex, fibrosis of the interstitial tissue, significantly decreased number of glomeruli, severer podocyte foot process fusion (4. 20 ± 1. 08% vs 86.79 ± 1. 66%) , markedly increased PAX2 (1. 43 ± 0. 09 vs 2. 44 ± 0. 09) and decreased VEGF expressions (0. 80 ± 0. 15 vs 0. 33 ± 0. 14). However, in the decompressed kidneys, the cystic changes decreased, number of glomeruli increased, but extracellular matrix (ECM) deposition was still obvious, fusion of the podocyte foot processes was reduced (41. 18±3. 13% vs 86. 79± 1. 66%), VEGF expression was significantly increased (2. 08 ± 0. 21 vs 0. 33 ± 0. 14) , and expression of PAX2 was restored to some extent (2. 05 ± 0. 14 vs 2. 44 ± 0. 09) in decompressed kidneys. Conclusions Relief of obstruction in utero can reverse the development of nephropathy, evidenced by the phenotype transformation of podocytes, expression of PAX2 and VEGF.     

胎羊单侧输尿管不完全性梗阻后肾脏足细胞表型转化及PAX2、VEGF的表达

Objective To investigate the phenotypic change of the podocytes and paired box gene 2 (PAX2) and vascular endothelial growth factor (VEGF) expressions in fetal lambs' kidneys with unilateral partial ureteral obstruction. Methods Sixteen fetal lambs were randomly assigned to the obstruction and control group. The obstruction group included 12 lambs, whose superior segment ureters were tied with splited silastic tube to induce unilateral partial ureteral obstruction between 75and 85 gestational days. The control group had 4 fetal lambs subjected to sham operation. After birth,the kidneys of the lambs were harvested to study the phenotypic change of the podocytes as well as expressions of PAX2 and VEGF in the kidneys. Results Nine out of the 12 lambs of the obstruction group were delivered alive. All 4 sham operated lambs were delivered alive. Renal cortex cysts of varying sizes, interstitial fibrosis, a decrease in glomeruli number, and severe podocyte foot process fusion (4. 20± 1.08% vs 86. 79 ± 1.66%) were found in the obstructed kidneys compared with the control kidneys. The PAX2 expression in obstructed kidneys was significantly higher than that of the control kidneys (1.43 ± 0. 09 vs 2. 44 ± 0. 09, P＜0. 05). The VEGF expression was significantly decreased compared with the control kidneys (0. 80 ± 0. 15 vs 0. 33 ± 0. 14, P＜0. 05). Conclusions The changes of the phenotype and PAX2 and VEGF expressions may play roles in the pathogenesis of obstructive nephropathy.     

胎羊单侧输尿管不完全性梗阻后肾脏足细胞表型转化及PAX2、VEGF的表达

目的 研究胎羊单侧输尿管不完全性梗阻后肾脏的组织学改变,探讨梗阻性肾病的发生机制.方法 以16只胎羊为研究对象.实验分两组:①梗阻组,对12只孕75～85 d的胎羊实行宫内手术,F6 C形硅胶环环套在胎羊一侧输尿管上段以造成输尿管不完全性梗阻;②对照组,对4只胎羊实行宫内手术但不结扎输尿管.待胎羊出生后,取其肾脏标本检测病理改变,足细胞表型转化以及配对盒基因2(PAX2)和VEGF的表达变化.结果 梗阻组12只胎羊,其中9只顺利生产;对照组4只胎羊,均顺利生产.与对照组羔羊肾脏相比,梗阻组羔羊梗阻侧肾脏,表现为皮质囊性改变,间质纤维化,肾小球数目显著减少;足细胞足突广泛融合[(4.20±1.08)%比(86.79±1.66)%];PAX2表达显著升高(1.43±0.09比2.44±0.09);而VEGF表达明显减少(0.80±0.15比0.33±0.14).结论 在胎羊模型中,通过观察单侧输尿管不完全性梗阻后肾脏的组织学改变,说明足细胞表型转化以及PAX2和VEGF表达的变化可能在梗阻所致的肾脏损伤性改变中占有重要作用.     

小儿肾积水尿细胞因子IGF-1、ET-1、TGF-β1及MCP-1水平的检测及意义

Objective To evaluate clinical significance of urinary cytokines in evaluating the damage severity of affected kidneys in children with hydronephrosis. Methods The pyelic urinary in-sulin-like growth factor-1 (IGF-1), endothelin-1 (ET-1), transforming growth factor-β1 (TGF-β1) and monocyte chemoattractant protein-1 (MCP-1) in affected and healthy kidneys (as controls) were de-tected in 41 children with congenital hydronephrosis by enzyme-linked immuno-sorbent assay (ELISA). Pathologic changes of the affected kidneys were graded and the correlations of pathologic grades with urinary level of IGF-1, ET-1, TGF-β1 and MCP-1 were analyzed by Spearman's test. Re-sults The level of urinary IGF-1 in healthy group was (279. 45 ± 31.57) pg/ml, which was signifi-cantly higher than that in hydronephrosis group ( ( 186. 69 ± 24. 63) pg/ml). However, the levels of u-rinary ET-1, TGF-β1 and MCP-1 in healthy group was significantly less than those in hydronephrosis group ((13.21±2.91 vs 49.81 ±9.08) pg/ml, (232.57±32.68 vs 395.91 ±83.52) pg/ml and (328. 54 ± 36. 81 vs 486. 59 ± 89. 72) pg/ml, respectively). Negative correlation was noted between u-rine IGF-1 levels and pathologic grades (P<0. 01 ). Conclusions Urinary IGF-1 is an ideal marker in evaluating the damage severity of affected kidneys in children with hydronephrosis.     

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.     

Two approaches for newborns with critical congenital heart disease: a comparative study

Background Prenatal diagnosis and planned peripartum care is an unexplored concept in China.This study aimed to evaluate the effects of the“prenatal diagnosis and postnatal treatment integrated model”for newborns with critical congenital heart disease.Methods The medical records of neonates(≤28 days)admitted to Fuwai Hospital were reviewed retrospectively from January 2019 to December 2020.The patients were divided into“prenatal diagnosis and postnatal treatment integrated group”(n=47)and“non-integrated group”(n=69).Results The age of admission to the hospital and the age at surgery were earlier in the integrated group than in the non-integrated group(5.2±7.2 days vs.11.8±8.0 days,P<0.001;11.9±7.0 days vs.16.5±7.7 days,P=0.001,respectively).The weight at surgery also was lower in the integrated group than in the non-integrated group(3.3±0.4 kg vs.3.6±0.6 kg,P=0.010).Longer postoperative recovery time was needed in the integrated group,with a median mechanical ventilation time of 97 h(interquartile range 51–259 h)vs.69 h(29–168 h)(P=0.030)and with intensive care unit time of 13.0 days(8.0–21.0 days)vs.9.0 days(4.5–16.0 days)(P=0.048).No significant difference was observed in the all-cause mortality(2.1 vs.8.7%,P=0.238),but it was significantly lower in the integrated group for transposition of the great arteries(0 vs.18.8%,log rank P=0.032).Conclusions The prenatal diagnosis and postnatal treatment integrated model could significantly shorten the diagnosis and hospitalization interval of newborns,and surgical intervention could be performed with a lower risk of death,especially for transposition of the great arteries.     

外源性血管内皮生长因子基因对新生鼠缺氧缺血性脑损伤脑细胞凋亡的影响

Objective To explore the effect of exogenesis VEGF 120 gene on the apoptosis of brain cells in the HIBD of newborn rats. Methods VEGF eukaryotic expression plasmid (pCDNA 3.1/r VEGF 120) was constructed by cloning rat VEGF 120 cDNA into eukaryotic expression vector pCDNA 3.1. The HIBD model was established with seven days old SD rats,and all rats were diveded into two groups at random :contral group 18 rats( every rat model was injected pCDNA 3.1 100 μg immediately after hypoxia-is-chemic.then raised seven days) and therapy group 18 rats (every rat model was injected pCDNA 3.1/ rVEGF 120 100 μg immediately after hypoxia-ischemic). Flow cytometer( FCM) was used to detect the ratio of apoptosis of brain cell. Results There was a significant decrease in the ratio of apoptosis brain cells( control group 17.505 ± 0.949; therapy group 8.93 ± 0. 332). Conclusion The VEGF gene product can reduce apoptosis of brain cells.     

外源性血管内皮生长因子基因对新生鼠缺氧缺血性脑损伤脑细胞凋亡的影响

Objective To explore the effect of exogenesis VEGF 120 gene on the apoptosis of brain cells in the HIBD of newborn rats. Methods VEGF eukaryotic expression plasmid (pCDNA 3.1/r VEGF 120) was constructed by cloning rat VEGF 120 cDNA into eukaryotic expression vector pCDNA 3.1. The HIBD model was established with seven days old SD rats,and all rats were diveded into two groups at random :contral group 18 rats( every rat model was injected pCDNA 3.1 100 μg immediately after hypoxia-is-chemic.then raised seven days) and therapy group 18 rats (every rat model was injected pCDNA 3.1/ rVEGF 120 100 μg immediately after hypoxia-ischemic). Flow cytometer( FCM) was used to detect the ratio of apoptosis of brain cell. Results There was a significant decrease in the ratio of apoptosis brain cells( control group 17.505 ± 0.949; therapy group 8.93 ± 0. 332). Conclusion The VEGF gene product can reduce apoptosis of brain cells.     

维生素E拮抗邻苯二甲酸二(2-乙基)己酯尿道发育毒性的实验研究

目的 探寻维生素E(Vitamin E,VitE)对邻苯二甲酸二(2-乙基)己酯[Di(2-ethylhexy1)phthlate,DEHP]所致大鼠尿道发育毒性的拮抗作用及其可能机制.方法 GD12(gestation day12)SD孕鼠随机分为4组,每组20只:玉米油对照组、DEHP组(500 mg·kg-1·d-1)、DEHP(500mg·kg-1·d-1)+VitE(200mg·kg-1·d-1)组和VitE组(200mg·kg-1·d-1).各组分别于母鼠孕期12～19d(GD12～19)持续经口灌注给药.各组分别留取10只孕鼠让其正常分娩,出生第一天,即对新生大鼠计数,并在解剖显微镜下测量雄性新生鼠的肛门生殖器距离(anal genital distance,AGD)并称体重;雄性仔鼠70日龄时逐个检查尿道下裂的发生情况.余孕鼠在GD19d行破宫产取仔代鼠,应用逆转录-聚合酶链反应(RT-PCR)的方法检测胎鼠阴茎TGF-β1,TGF-βR3 mRNA的表达水平.DNA末端原位标记染色法(TUNEL法)检测胎鼠阴茎尿道上皮细胞凋亡情况.结果 各组TGF-β1mRNA表达水平分别为:正常组为0.63±0.07、DEHP组为0.96±0.12、DEHP+VitE组为0.65±0.07、VitE组为0.62±0.06,DEHP组表达明显较其他各组增高(P＜0.05).各组TGF-βR3mRNA表达水平分别为:正常组为0.47±0.10、DEHP组为0.75±0.10、DEHP+VitE组为0.49±0.09、VitE组为0.46±0.09,DEHP组表达明显较其他各组增高(P＜0.05).各组胎鼠阴茎凋亡指数分别为:正常组为(30±2.0)%、DEHP组为(8.8土1.1)%、DEHP+VitE组为(28.9±1.6)%、VitE组为(29.6±2.0)%,DEHP组凋亡细胞数较其他各组相比明显减少,差异有统计学意义(P＜0.01).导致大鼠尿道下裂的发生.VitE可降低DEHP上调的胎鼠阴茎TGF-β1,TGF-βR3 mRNA表达水平,恢复胎鼠阴茎尿道上皮细胞的凋亡水平.结论 VitE对DEHP所致尿道发育毒性具有拮抗作用,其机制可能与调控TGF-βs及胎鼠阴茎尿道上皮细胞的凋亡有关.

Abstract：

Objective To study the therapeutic effects of Vitamin E (VitE) on urethral development toxicity induced by di(2-ethylhexyl) phthalate (DEHP). Methods From gestational day 12 to gestational day 19 (GD 12-19) , the timed-pregnant Sprague-Dawley (SD) rats were fed with the eiwith 20 in each group: DEHP group, DEHP + VitE group, and VitE group. The control rats were fed with corn oil. Ten pregnant rats of each group delivered full-term infant rats. The male infant rats were counted, and the anal genital distance (AGD) and body weight were measured. Hypospadias morbidity was also counted on male rats after 17 postnatal days. In the rest 10 pregnant rats of each group, fetuses were harvested on GD19. Semi-quantitive RT-PCR was used to measure mRNA expression of TGF-β1 and TGF-βR3. TUNEL staining was used to measure cell apoptosis in the fetus' genital tubercles. Results Hypospsdias was observed in male rat after 17 postnatal days. The TGF-β1 mRNA of the control group, DEHP group, DEHP + VitE group, and VitE group is 0. 63 ± 0. 07,0. 96±0. 12, 0. 65 ±0. 07, and 0. 62± 0. 06, respectively. The TGF-βR3 mRNA of the control group,DEHP group, DEHP + VitE group, and VitE group was 0. 47 ± 0. 10, 0. 75 ± 0. 10, 0. 49 ± 0. 09,and 0. 46 ± 0. 09, respectively. The TGF-β1 mRNA and TGF-βR3 mRNA was up-regulated in the fetus of DEHP group (P＜0. 05). Cell apoptosis rate in fetus' genital tubercles on GD19 of the control group, DEHP group, DEHP + VitE, and VitE group was 30% ± 2. 0%, 8. 8% ± 1.1%, 28. 9% ±1.6%, and 29. 6% ± 2. 0%, respectively. Cell apoptosis rate was significantly reduced in the fetus of DEHP group (P＜0. 01). In the GD19 fetus treated with VitE, hypospadias morbidity, the TGF-β1 and TGF-βR3 mRNA expressions were significantly decreased. And cell apoptosis rate was significantly increased. Conclusions Vitamin E ameliorates the urethral development toxicity induced by DEHP via regulating TGFβs expression and cell apoptosis in rat fetus.     

成纤维细胞生长因子受体4在人发育肾和病理肾中的表达

目的：观察成纤维细胞生长因子受体4(Fibroblast growth factor receptor4, FGFR4) 在人发育肾组织和儿童常见肾脏疾病中的表达,研究成纤维细胞生长因子（Fibroblast growth factor, FGF）及其受体(FGFR4)在人发育肾和病理肾中的作用,为肾脏病理发生机制研究提供新思路。方法：采用免疫组化法分析FGFR4在18例8~34周龄胎儿肾组织和82例儿科常见肾脏疾病,包括原发性肾病综合征、急性肾炎、紫癜性肾炎、单纯性血尿的表达,并作与肾脏病理积分的相关性分析。结果：①肾发生带内FGFR4表达微弱,肾囊泡和S 型小体的上支和中间支,即原始肾小管上皮细胞部位有微弱表达,间充质、压缩间充质细胞未见表达,输尿管芽及其末端壶腹和C-期足细胞表达不明显。M-期肾小球和近端小管无阳性细胞染色,远端小管和集合管表达较为明显。②所有病理切片均存在FGFR4不同程度阳性的表达,较正常对照组明显增加,其中肾小球区表达微弱,主要在足细胞部位;肾小管区表达较为强烈,主要部位在远端小管,表达密集部位的小管结构明显异常,表现为细胞萎缩、管腔扩大,尤其部分近端小管更为明显。③原发性肾病综合征与其他3种肾脏疾病的各部位FGFR4表达均未见明显差异(P>0.05)。肾近端小管和远端小管各病理类型间FGFR4表达差异无显著性,足细胞FGFR4表达在紫癜性肾炎组明显高于其他各病理类型组( P<0.05)。④相关性分析发现,近端小管FGFR4表达与肾小管病理积分呈正相关,其他各部位表达均与病理积分呈负相关（均P<0.05）。结论：FGF-FGFR4对早期肾单位的形成可能不起关键作用,而是与其后期较成熟阶段肾小管和集合管发育的调控有关。FGFR4可能参与儿童原发性肾病综合征、急性肾炎、紫癜性肾炎、单纯性血尿的病理发生,表达程度增多与肾脏病理损害有一定关系,表达适度增多有利于足细胞和肾小管损伤修复,过表达则可能加重病理损害。［中国当代儿科杂志,2007,9（2）：133-138］     

沉默PAX2基因对肾间质纤维化大鼠的影响

目的 探讨体内沉默PAX2基因对肾间质纤维化大鼠肾小管上皮细胞转分化(EMT)的影响。方法 64只Wistar大鼠麻醉后,单侧输尿管结扎法制作肾间质纤维化大鼠模型,随机分为阴性对照组和PAX2基因沉默组,每组32只。将200 μL NC-siRNA-in vivo jetPEITM混合液转染阴性对照组大鼠,将200 μL PAX2-siRNA-in vivo jetPEITM混合液转染PAX2基因沉默组大鼠,各组分别于转染后3、5、7、14 d分为4个亚组,每组8只。留取各组肾组织标本,应用Real-Time PCR及Western blot法检测肾皮质PAX2 mRNA及其蛋白的沉默情况,以及E-钙粘连素(E-cadherin)、α-平滑肌肌动蛋白(α-SMA)mRNA和蛋白表达情况。结果 PAX2基因沉默组PAX2 mRNA和蛋白表达量较阴性对照组均降低 (P < 0.05)。随着梗阻时间的延长,两组E-cadhelin mRNA和蛋白表达量逐渐下降,α-SMA mRNA和蛋白表达量逐渐升高;在转染14 d时,PAX2基因沉默组E-cadhelin mRNA和蛋白相对表达量明显高于阴性对照组 (P < 0.05),而α-SMA mRNA和蛋白相对表达量明显低于阴性对照组 (P < 0.05)。结论 沉默PAX2基因在肾间质纤维化晚期大鼠中可明显抑制肾小管EMT进程,可能对肾间质纤维化有治疗作用。     

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。     

Evaluation of complete and partially obstructed kidneys using Gd-DTPA enhanced dynamic MRI in adolescent swine

PURPOSE: Aim of this study was to evaluate the dynamic changes in renal relative signal intensity (RSI) following the administration of Gd-DTPA in adolescent pigs with complete and partial unilateral ureteric obstruction. METHODS: Pigs were divided into 3 groups: partial and complete unilateral ureteric obstruction and controls. Complete unilateral ureteric obstruction (CUUO) was created by ligating the left ureter, whereas partial unilateral ureteric obstruction (PUUO) was created in pigs of 2 weeks of age by embedding the left ureter into the psoas muscle. Dynamic MRI was performed before and at 0 - 60 min after an intravenous bolus injection of Gd-DTPA. Mean RSI of the renal cortex, medulla and pelvis was measured and interpreted as an indirect measure of the renal function. In addition, renography was performed, and renal morphology was examined IN VITRO. RESULTS: Three phases of RSI were identified. The dynamic RSI patterns differed markedly between obstructed and control kidneys. In PUUO kidneys, Phase 1 of the mean RSI of the cortex and medulla demonstrated a decreased amplitude and prolonged duration, whereas in Phase 2 the mean RSI of the pelvis was increased. In acute CUUO kidneys, the mean RSI patterns were similar to those of controls, except for a significant increase of the pelvic mean RSI. CONCLUSIONS: Gd-DTPA enhanced dynamic MRI allowed a characterization and differentiation of renal function and morphology of normal and obstructed kidneys, and secondly, provided potentially important information on renal concentrative and filtration availability.     

输尿管梗阻大鼠肾脏肝细胞生长因子基因修饰的骨髓间充质干细胞移植

目的 观察携带肝细胞生长因子(HGF)基因的大鼠骨髓间充质干细胞静脉移植是否能够迁移、分布到单侧输尿管梗阻大鼠肾脏.方法 体外分离培养雄性大鼠骨髓间充质干细胞,并转染腺病毒-HGF (Ad-HGF),采用ELISA方法检测转染后HGF的表达情况;建立16只雌性单侧输尿管梗阻大鼠动物模型,随机分为移植组和对照组,移植组经鼠尾静脉注入Ad-HGF转染的骨髓间充质干细胞,对照组注入等量生理盐水,于术后7 d、14d取双侧肾脏,制作石蜡切片,Y染色体原位杂交方法检测雌性受体大鼠.肾脏中是否有骨髓间充质干细胞分布及分布情况.结果 移植组术后7 d梗阻侧肾脏可见Y染色体性别决定基因(Sty)阳性细胞,14d Sry阳性细胞数明显减少(P<0.05),主要分布在肾小管上皮细胞区,肾小球区未见Sry阳性细胞,而梗阻对侧及对照组双侧肾脏未见Sry阳性细胞.结论 鼠尾静脉移植携带HGF基因的骨髓间充质干细胞能够定居于输尿管梗阻侧肾脏,并分布到肾小管上皮细胞区.     

血管紧张素Ⅱ对幼鼠输尿管梗阻后AQP2表达变化的调控

目的 通过观察血管紧张素Ⅱ(angiotensin Ⅱ,ANG Ⅱ受体阻滞剂坎地沙坦对双侧输尿管梗阻(bilateral ureteral obstruction,BUO)幼鼠肾脏水通道蛋白2(aquaporin 2,AQP2)表达的影响,探讨ANG Ⅱ对梗阻肾脏功能和AQP2的调控作用。方法 24只慕尼黑幼鼠随机分为BUO组、坎地沙坦干预组(BUO+ CAN)和对照组(Sham),每组n=8只。BUO组和BUO+ CAN组均行双侧输尿管结扎,并采用微型泵分别给以生理盐水和坎地沙坦,Sham组仅游离输尿管但不结扎,24h后解除梗阻并继续观察48h后收集血液和肾脏标本,采用免疫印记技术检测肾脏AQP2表达水平。结果 梗阻解除后BUO组与Sham组相比尿量显著增高,(92±7)μl·min-1 ·kg-1比(25±3)μl· min-1·kg-1、尿渗透压显著降低,(636±55) mosmol/kgH2O比(1 853±163) mosmol/kgH2O、血浆渗透压和血浆醛固酮均显著增高,分别为(336±10) mosmol/kgH2O比(303±7)mosmol/kgH2O和(4.1±0.2)nmol/L比(1.4±0.1)nmol/L;肾脏AQP2表达下调到Sham组17％各组比较差异有统计学意义,P＜0.05。BUO+ CAN组与BUO组相比尿量显著减少,(55±5)μl·min-1 ·kg-1比(92±7)μl·min-1 ·kg-1,尿渗透压显著增高(783±47) mosmol/kgH2O比(636±55) mosmol/kgH2O,血浆醛固酮含量显著降低(2.8±0.5) nmol/L比(4.1±0.2)nmol/L,肾脏AQP2表达增高,各组比较差异有统计学意义,P＜0.05。结论 ANG Ⅱ受体拮抗剂可通过阻止AQP2下调纠正水代谢紊乱,保护肾功能,提示ANG Ⅱ通过调节肾脏AQP2表达参与输尿管梗阻后肾脏水代谢变化。     

Intrauterine growth restriction modifies the normal gene expression in kidney from rabbit fetuses

The aim of this work was to study the effect of intrauterine growth restriction (IUGR) on fetal kidneys. The IUGR was induced by uteroplacental vessels ligature in a model of pregnant rabbit. We centralized the study in the gene expression of essential proteins for fetal kidney development and kidney protection against hypoxia, osmotic stress, and kidney injury. The gene expression of HIF-1α, NFAT5, IL-1β, NGAL, and ATM were studied by qRT-PCR and Western blot in kidneys from control and IUGR fetuses. Experimental IUGR fetuses were significantly smaller than the control animals (39 vs. 48 g, p < 0.05). The number of glomeruli was decreased in IUGR kidneys, without morphological alterations. IUGR increased the gene expression of HIF-1α, NFAT5, IL-1β, NGAL, and ATM (p < 0.05) in kidneys of fetuses undergoing IUGR, suggesting that fetal blood flow restriction produce alterations in gene expression in fetal kidneys.     

Gd-DTPA增强动态核磁共振诊断输尿管不全梗阻的实验研究

目的：探讨Gd-DTPA增强动态核磁共振成像（MRI）诊断输尿管不全梗阻的意义。方法：将新生鼠输尿管交界处理于腰大肌中制成输尿管不全梗阻模型（n=10)。1年后用Gd-DTPA增强动态MRI检查梗阻组和对照组（n＝12）鼠的肾脏，并对不同时间记录的肾脏影像进行分析，计算出肾皮质，髓质和肾盂的相对信号强度。结果：使用Gd-DTPA后，对照组肾后质，髓质和肾盂信号强度相继减弱，30－60min后基本恢复，梗阻肾脏的变化明显较对照组慢，60min后仍未恢复。结论Gd-DTPA增强动态MRI可用于诊断输尿管不全梗阻并提供肾功能变化信息。