两侧肾静脉肾素比值评价肾动脉支架植入术治疗单侧肾动脉狭窄

目的探讨肾静脉肾素活性及患侧肾静脉肾素与对侧肾静脉肾素的比值（RVRR）对肾动脉狭窄介入治疗高血压疗效的预测价值。方法72例合并高血压的肾动脉狭窄，根据术前RVRR水平分为≥1．5组（51例）和RVRR〈1．5组（21例）。予肾动脉支架植入术（PTRA），手术前后测定肾静脉肾素活性，并对患者进行1年的随访。结果RVRR≥1．5组PTRA后3个月、6个月及1年对高血压治疗无效率分别为3．92％、2．0％及2．0％。但RVRR〈1．5组均高达76．2％。结论对于单侧肾动脉狭窄患者，肾静脉肾素水平及RVRR对预测PTRA治疗高血压的疗效有重要价值。     

肝细胞导向的促红细胞生成素基因转移在肾性贫血基因治疗的初步研究

目的探索用受体介导方法对肾性贫血基因治疗的可行性及疗效。方法构建一种克隆了促红细胞生成素（ＥＰＯ）基因的ＥＢＶ复制子载体ｐＥＰＯ，该载体与半乳糖基化组蛋白结合形成可溶性的核酸蛋白复合物，以静脉注射的方式将复合物导入通过喂饲腺嘌呤造成肾性贫血大鼠，恢复正常饮食２周后，采血样检测血红蛋白的含量和红细胞数，并与对照组进行比较。结果注射ｐＥＰＯ复合物组的红细胞数和血红蛋白含量都有明显升高，实验组和对照组的红细胞数分别为每毫升４９２个和４０７个；血红蛋白含量分别１１．４ｇ／ｍｌ和９．１ｇ／ｍｌ。两组比较，Ｐ＜０．０１。提示ＥＰＯ基因已被导入动物体内并表达出目的蛋白，但肾衰症状并不改善。结论以上结果证明通过受体介导的基因转移技术可将ＥＰＯ基因导入实验动物体内并进行表达，改善肾性贫血     

A comparison of the effects of renal artery constriction and anemia on the production of erythropoietin

It is generally assumed that the O₂ supply to the kidneys is the major determinant of the synthesis of erythropoietin (Ep). In the present study, the O₂ supply of the kidneys of rats was lowered by the reduction of renal blood flow (rbf). Plasma Ep was determined after about 18 h of bilateral application of Goldblatt clips with graded inner diameters. The results were compared to findings in anemic rats, in which the systemic O₂ supply was lowered by exchange transfusion of blood with plasma. We found a linear correlation between Ep levels in plasma and the degree of reduction of rbf. However, there was an exponential relationship between Ep levels and the concentration of hemoglobin in blood. In addition, the elevation of plasma Ep was only moderate, when rbf was reduced (maximum 0.07 IU Ep/ml plasma). The increase in Ep concentration was much more pronounced in anemia (up to about 7 IU Ep/ml plasma). From these results it may be concluded that decreasing oxygen supply to the kidney through reduction in renal blood flow (ischemic hypoxia) is less effective in increasing erythropoictin production than reducing the hemoglobin concentration (anemic hypoxia). The possibility must be considered that the increase in renal production of erythropoietin due to anemic hypoxia is triggered by one or more extrarenal signals.A preliminary report on the production of erythropoietin in anemic rats was presented at the XIth Int. Berlin Symposium on Erythroid Cells (Biomed Biochim Acta 46:S 304–S 308, 1987)     

Prevalence and severity of atherosclerosis in renal artery in Northwest Indian population: an autopsy study

Background  Atherosclerosis has been described as the most common cause of renal artery stenosis. The purpose of this autopsy study was to assess the preponderance and severity of atherosclerotic changes in renal artery in different age groups in normal population. Methods  Ninety renal arteries from 45 cadavers above 30 years of age were obtained at autopsy. Fifty-four renal arteries were studied grossly after Sudan IV staining for extent and severity of fatty deposits in terms of Atherosclerotic index (AI). Another 36 renal arteries were studied microscopically for changes in different layers and at different sites of artery and luminal narrowing, if any with advancing age. Results  In grossly stained specimens, incidence and AI which is the marker of extent and severity of lesions were found to increase gradually with advancement of age. Increased incidence of atherosclerotic changes with better nutritional status was recorded. In microscopically studied specimens, intimal thickness which is a marker of disease also showed upward rise with advancing age. Renal artery stenosis was prevalent in 13.8% cases. Lesions were most commonly detected at renal ostium and proximal segment. Conclusions  Fatty changes appear with advancing age. Advanced types of changes including fibrous plaques, calcification and ulceration were noticed first in fifth decade. The changes were usually bilateral. Proximal segment was the most affected part. Four cases had less than 50% and one case had 70% luminal narrowing. The changes were only moderately severe in most of the cases.     

Ultrastructural pathological features of unilateral renal artery stenosis in the rats

Renal artery stenosis (RAS) is one of the main reasons of renovascular hypertension and its pathogenesis remains unclear. In this study, we aimed to investigate histopathological characteristics in a rat model of RAS. Sprague-Dawley (SD) male rats were randomly divided into unilateral RAS group (Model group, n = 30) and Sham group (n = 30). The left renal artery was clamped with miniature silver clip for the rats in RAS group, while it was exposed but not clamped for the rats in Sham group. After the surgery, the rats were randomly divided into ten subgroups based on the time after surgery (n = 3). Blood pressure, urinary albumin/creatinine ratio, and serum albumin and creatinine levels were measured. The kidneys were dissected for histological and electron microscopy analysis. The results showed that systolic blood pressure was significantly higher since 4 weeks after surgery compared to before surgery. There were no significant differences in urinary albumin/creatinine ratio as well as serum albumin and creatinine levels in Model and Sham groups. During the early acute renal ischemia the stenotic kidney exhibited acute tubular injury, podocyte injury and some crescent formation, and the main components of crescent are podocytes. Although renal tubules and vascular lesions gradually recover and crescent disappears, segmental lesions of podocyte appear in the late stage of RAS. These data reveal ultrastructural pathological changes during RAS, and suggest the role of podocyte lesions in chronic renal ischemia.     

Influence of hepatic innervation on renal glomerular filtration rate

Electrical stimulation of perivascular portal nerves leads to rapid, transient increase of renal glomerular filtration rate (GFR) and of urinary flow rate ( ). In contrast, perivascular stimulation at the vena cava inferior does not significantly alter GFR and . Spinal transfection at the thoracocervical junction does not significantly modify the effect of periportal nerve stimulation. Infusion of the -adrenergic agonist phenylephrine (20 nmol/min) into the superior mesenteric vein increases GFR and , whereas infusion of identical amounts of phenylephrine (20 nmol/min) into the jugular vein does not significantly alter GFR or . The observations indicate that -adrenergic innervation of the liver modifies renal function.     

Myoglobin expression in renal cell carcinoma is regulated by hypoxia

Myoglobin is a member of the hemoprotein superfamily, which additionally includes hemoglobin, neuroglobin and cytoglobin. Cytoplasmic localized myoglobin functions as a radical scavenger and prevents hypoxia. Besides muscle tissue MB expression could also be observed in other tissues as well as in different types of cancer.     

In vivo carbon monoxide exposure and hypoxic hypoxia stimulate immediate early gene expression

 This study aimed to examine the influence of acute tissue hypoxygenation on the expression of immediate early genes in different rat tissues. To this end male Sprague-Dawley rats were exposed to 0.1% carbon monoxide for 0.5, 1 and 6 h or to 9% oxygen for 6 h and mRNA levels for c-jun, c-fos, c-myc and EGR-1 were assayed by RNase protection in hearts, kidneys, livers and lungs. We found that hypoxia increased c-jun mRNA levels between twofold (lung) and eightfold (liver) in all organs examined; c-fos mRNA increased between threefold (lung) and 20-fold (heart); c-myc mRNA increased between twofold (lung) and sixfold (heart); and EGR-1 mRNA increased between twofold (lung) and sixfold (heart). Our findings suggest that acute tissue hypoxygenation is a general stimulus of the expression of immediate early genes in vivo. With regard to the sensitivity to hypoxia, organ differences appear to exist in that the lung is rather insensitive, whilst the heart is rather sensitive. Received: 25 February 1997 / Received after revision: 17 June 1997 / Accepted: 19 June 1997     

慢性间歇性低氧对大鼠肾脏氧化应激损伤及HIF-1α表达的影响

目的:观察慢性间歇性低氧(CIH)大鼠肾组织形态学及其氧化应激相关指标变化,探讨CIH的肾损害机制。方法:将40只SD大鼠随机分为4组,CIH组2周和4周组(2IH和4IH)以及对照组2周和4周组(2C和4C),每组10只,采用化学比色法检测血清SOD活性,肾脏称重计算肾体比,HE染色、PAS染色和Masson染色法观察肾组织病理结构变化,real-time PCR法检测肾组织HIF-1α、Cu/Zn SOD和Mn SOD mRNA的表达变化。结果:(1)各组大鼠平均肾重、体重和肾体比差异无统计学意义(均P0.05);IH组大鼠肾组织存在病理损害,HE和PAS染色示肾小球系膜和基底膜轻度增生,肾小管上皮水肿,4周组损害较明显;Masson染色IH和对照组均未见纤维化改变。(2)化学比色法示IH组血清SOD活性低于相应对照组(均P0.05),4IH组下降更明显(P0.05)。Cu/Zn SOD和Mn SOD mRNA组间比较差异有统计学意义(均P0.05);Cu/Zn SOD mRNA表现为IH组低于相应对照组(均P0.05),4IH组与2IH组比较差异无统计学意义;Mn SOD mRNA的表达4IH组较4C组下调,差异有统计学意义(P0.05),4IH组明显高于2IH组(P0.05),2IH和2C组比较差异无统计学意义(P0.05)。IH组肾组织HIF-1α的mRNA表达均高于相应对照组(均P0.05),4IH组高于2IH组(P0.05)。结论:CIH可诱导大鼠肾小球、小管结构异常,但4周CIH尚未引起肾组织纤维化改变。CIH可通过上调HIF-1αmRNA和下调Cu/Zn SOD、Mn SOD mRNA的表达,参与氧化应激损伤过程。     

内皮素在急性肝衰竭时肾功能障碍发生中的作用

目的：探讨内皮素在急性肝衰竭时肾功能障碍发生中的作用。方法：对硫代乙酰胺（ＴＡＡ）诱导的急性肝衰竭大鼠肝肾功能及内皮素水平进行动态观察。结果：随着肝损伤的加重，肾功能亦进行性恶化（表现为血肌酐升高，肌酐清除率下降，尿量减少，尿钠分泌降低等），血浆内毒素逐渐升高，均于４８ｈ最为严重。伴随上述变化，肾组织内皮素活性渐升高，亦于４８ｈ达高峰。血浆内皮素和肌酐清除率及肌酐清除率与肾组织内皮素水平之间均呈显     

Homocysteine and atheromatous renal artery stenosis

Hyperhomocysteinemia is an independent risk factor for vascular disease, frequently observed in patients with severe renal impairment. Hyperhomocysteinemia has never been considered as a possible risk factor in renal artery stenosis. We investigated plasma folate and vitamin B₁₂, methylenetetrahydrofolate reductase (MTHFR) C577T and cystathionine β-synthase (CBS) 844ins68 polymorphisms, and homocysteine levels before and after methionine (100 mg/kg) loading in 58 patients with angiographically documented renal artery stenosis and mildly impaired renal function. One hundred and two normotensive subjects with angiographically normal coronary arteries and no history or clinical or angiographic evidence of atherosclerosis in other vascular districts, were considered as a control group. Mean total homocysteine levels were significantly higher in patients than in controls (P<0.01), as was the prevalence of hyperhomocysteinemia (51.7% vs. 32.3%, P<0.05). However, MTHFR alleles and genotypes as well as CBS 844ins68 mutation frequencies were similar in the two groups, whereas a lower folate level was observed in the patients. Moreover, patients with MTHFR A/A genotype showed a poorer folate status than control subjects, suggesting that a subclinical folate deficiency may be very frequent in renal artery stenosis, regardless of C677T mutation. In conclusions, hyperhomocysteinemia is common in patients with atheromatous renal artery stenosis; a subclinical folate deficiency seems to be involved, regardless of MTHFR thermolabile or CBS insertion genotypes. Folate supplementation might be useful in the management of overall vascular risk of these patients. Received: 13 November 2001 / Accepted: 13 December 2001     

红细胞生成素3'-增强子片段对内皮细胞缺氧时环加氧酶-2基因表达的影响

目的和方法：体外合成红细胞生成素（Ｅｐｏ）３′－增强子野生型及突变型片段，借助脂质体，转入内皮细胞，用半定量ＲＴ－ＰＣＲ方法测定分离细胞在常氧或缺氧条件下培养４ｈ的环加氧酶２（ＣＯＸ－２）ｍＲＮＡ。结果：（１）大鼠主动脉内皮细胞、肺微血管内皮细胞在常氧下培养，有ＣＯＸ－２基因表达；（２）缺氧能诱导这两种细胞ＣＯＸ－２基因表达增加；（３）野生型Ｅｐｏ３′－增强子片段能阻断缺氧对内皮细胞ＣＯＸ－２基因表达的诱导作用，而突变片段则无此作用。结论：在ＣＯＸ－２基因序列中，可能存在Ｅｐｏ３′－端增强子片段，它参与了内皮细胞的缺氧反应     

Erythropoiesis and erythropoietin levels in renal transplant recipients

Summary Moderately increased blood levels of endogenous erythropoietin (Epo) usually induce complete restoration of renal anemia after successful kidney transplantation. With good graft function erythropoiesis is maintained by normal Epo serum levels. Persistent anemia can be related to iron deficiency, low excretory graft function, and high dosage of immunosuppressive agents leading to marrow suppression or nephrotoxicity. Acute early rejection is associated with a fall in serum Epo and abrogation of reticulocytosis. About 15% of recipients fail to exhibit the normal feedback regulation and develop a mostly transient post-transplant erythrocytosis. Both an increased sensitivity of erythrocytic progenitors to Epo and inappropriate Epo secretion by the native kidneys may account for this overshooting reaction.Abbreviations Epo erythropoietin - rHuEpo recombinant human erythropoietin - RIA radioimmunoassay - ELISA enzyme-linked immunosorbent assay - RTx renal transplantation - CAPD continuous ambulatory peritoneal dialysis - PTE posttransplant erythrocytosis - Aza azathioprine - CsA cyclosporine A - ALG antilymphoblast globulin     

慢性缺氧对大鼠肺内动脉平滑肌细胞Kv1.3、Kv2.1、Kv3.1钾通道基因在急性缺氧时表达的影响

目的与方法:用半定量RT-PCR方法,研究慢性连代缺氧对大鼠肺内动脉平滑肌细胞(PASMC)Kv13、Kv21、Kv31钾通道基因在急性缺氧时表达变化的影响。结果:①正常及慢性缺氧鼠PASMC中均有Kv13、Kv21、Kv31基因表达;②急性缺氧可使PASMC中Kv21、Kv31mRNA表达明显上调,其mRNA分别由0.646±0.092、0.782±0.104升高到1.059±0.134、0.985±0.116(P<0.01);③慢性缺氧后复氧12h再急性缺氧6h,PASMCKv21mRNA、Kv31mRNA水平均降低,其中Kv21mRNA由1.008±0.117下降到0.649±0.097,差异有极显著意义(P<0.01)。结论:Kv21、Kv31基因可能是缺氧反应基因,慢性缺氧可改变PASMC的Kv21、Kv31钾通道基因对急性缺氧的反应,使其由表达上调转变为下调,可能因而降低此钾通道在HPV中的作用。     

Prevalence of paraneoplastic erythropoietin production by renal cell carcinomas

The prevalence of increased serum immunoreactive erythropoietin (Epo) was determined in a prospective study of 49 patients with renal cell carcinoma. Measured by a monoclonal antibody based commercial enzyme-linked immunoassay, the Epo concentration was above the normal range, determined in nonanemic humans, in four of the renal carcinoma patients. Since three of these were anemic, their increased Epo level was considered to be appropriate. The high estimate of serum Epo (218 U/1) in the fourth patient, who was not anemic, was not confirmed when tested by radio immunoassay. Thus, in contrast with earlier studies, our results indicate that increased Epo is not a clear serological renal cell carcinoma marker. In addition, when monolayer cell cultures of 14 different established human renal carcinoma lines were screened, none of these released immunoreactive Epo in measurable amounts.Abbreviations Epo erythropoietin - ELISA enzyme-linked immunoassay - RIA radioimmunoassay     

红细胞生成素对慢性肾衰竭大鼠外周血内皮祖细胞SDF-1及其受体表达的影响*

 目的：观察红细胞生成素（EPO）对慢性肾衰竭（CRF）大鼠外周血内皮祖细胞（EPCs）归巢因子表达的影响。方法：采用分阶段5/6肾切除制备大鼠CRF模型。实验动物随机分为3组：假手术组、CRF组和EPO治疗组。从第3周开始,治疗组大鼠每次皮下注射重组人EPO 50 U/kg,每周3次,共6周。8周时取其外周血分离与培养EPCs,并检测EPCs的功能。采用实时荧光定量PCR和Western blotting检测外周血EPCs基质细胞衍生因子1 （SDF-1）及其受体（CXCR4）、EPO及其受体（EPOR）mRNA和蛋白的表达。结果：与CRF组比较,EPO治疗可上调外周血EPCs中SDF-1和CXCR4 mRNA及蛋白的表达（均P<0.05）;此外,EPO还可上调CRF大鼠外周血EPCs的 EPO及EPOR mRNA和蛋白的表达（均P<0.05）。结论：EPO对慢性肾衰竭大鼠外周血EPCs的动员可能与其增加外周血EPCs的 SDF-1及其受体表达有关。     

Loss of heterozygosity and protein expression of APC gene in renal cell carcinomas

This study evaluated the potential contribution of the APC gene to malignant transformation in patients with renal cell carcinoma. We tested 36 human renal cell carcinoma samples and 18 adjacent normal kidney tissues for the expression of APC protein, both wild and truncated types, by western blot using antibodies that recognize either the carboxy or the amino epitope of the APC protein. The same tumor samples together with autologous peripheral blood were also analyzed at the DNA level. Using specific oligonucleotide primers for exons 11 and 15, gene instability was followed by polymerase chain reaction/loss of heterozygosity (LOH) (on the basis of restriction fragment length polymorphism). Molecular data were also compared to pathohistological diagnosis, TNM stage, and patient’s age using multivariate statistical methods. All normal renal tissues revealed expression of the wild-type APC protein. Neither wild nor mutant type proteins were found in 36% (13/36) of tumor samples; the rest of tumor tissues expressed the wild-type protein (312 kDa). Mutated APC protein, with a molecular weight of 117 kDa, was found in only one tumor sample. From 36 tumor samples 16 (44.4%) were informative for RsaI exon 11 polymorphic site, while only half of these (8/16) demonstrated LOH. From 13 tumor samples that had no detectable protein product by western blot analysis eight were homozygous for the exon 11 polymorphism and were tested for another polymorphic site, MspI/exon 15. The overall proportion of LOH cases for both polymorphisms tested was 52.9% (9/17). Pathohistological diagnosis and molecular data showed no correlation. However, multivariate analysis determined a stage strong positive correlation of age and TNM with the presence of LOH and the absence of the wild-type APC protein. Out results suggest that the APC tumor suppressor gene plays a role in renal carcinogenesis. Alterations in this gene are responsible for tumor evolution and progression, but cannot be considered as a first event in tumor initiation. Received: 20 May 1998 / Accepted: 23 November 1998     

Morphometric analysis of renal arteries in patients with renal cell carcinoma

The aim of this study was to analyze morphometric parameters of renal arteries (longest diameter and tunica media thickness) in patients with renal cell carcinoma (RCC), to look into their relationship to tumor necrosis and to compare them with morphometric parameters recorded in a control group. We analyzed archival cases of RCC diagnosed in 2003 that also contained routinely sampled specimens of distal segments of renal artery. The control group consisted of specimens from both renal arteries obtained from 16 patients at routine autopsy during 2004-2005. Autopsy, as well as further histological analysis, did not disclose any malignant disease in the control group. Morphometric analysis of diameter and thickness of the renal artery tunica media was performed using Issa 3.1 software (Vamstek 2002, Zagreb, Croatia). The comparison of tunica media thickness showed that renal arteries from RCC cases were significantly thicker compared to distal parts of renal arteries in the control group (p=0.0002). Although renal artery samples from cases with necrotic tumor areas were thicker than those without tumor necrosis, the difference was not statistically significant. It is concluded that significantly thicker tunica media characterizes renal arteries in the group of patients with RCC when compared with the control group.