兔肾缺血再灌注损伤时TNF-α、IL-6和bFGF的变化及当归的影响

目的:探讨当归对兔肾缺血再灌注损伤的防治作用及其机制。方法:健康成年日本大耳白兔25只, 随机均分为假手术对照(control)组、单纯缺血再灌注(IR)组和缺血再灌注+当归(RAS+IR)组。在肾缺血1h再灌注48h后取肾组织作电镜检查, 并测血清肌酐(Cr)、肾组织肿瘤坏死因子(TNF-α)、白细胞介素-6(IL-6)和碱性成纤维细胞生长因子(bFGF)含量。结果:IR组肾组织变性改变显著, RAS+IR组病变轻微;IR组Cr、TNF-α和IL-6含量显著高于control组(P<0.05, P<0.05和P<0.01);RAS+IR组上述指标显著低于IR组。IR组bFGF含量显著低于control组(P<0.01), RAS+IR组bFGF含量显著高于IR组(P<0.01)和control组(P<0.05).结论:当归具有防治肾IR损伤的作用, 其机制可能与其对TNF-α、IL-6和bFGF等细胞因子的调控有关。     

Consanguinity-associated kidney diseases in Lebanon: an epidemiological study

Consanguineous marriages are common in many countries of the Middle East including Lebanon. Their impact on the repartition of kidney diseases and on the risk for familial nephritis is not known. We surveyed all of the dialysis centers in Lebanon. Nine hundred and twenty-five (925) patients and their private physicians were asked to answer a questionnaire. More than half of the hemodialysis (HD) patients had an unknown etiology of their kidney disease. Diabetes, polycystic kidney disease (PKD), chronic pyelonephritis and nephrosclerosis (NS) were the most commonly documented diagnoses. Consanguinity was present in 26% of the total HD population. More consanguineous patients with unknown renal etiology were diagnosed with their kidney diseases and initiated on dialysis before the age of 30 when compared with their non-consanguineous counter-parts (45% versus 33%, P<0.02 and 42% versus 27%, P<0.01), respectively. Similarly, consanguineous polycystic patients were diagnosed and started earlier on dialysis when compared with the non-consanguineous population (34% versus 12%, P<0.05 and 28% versus 8%, P<0.05), respectively suggesting a different disease pattern. Furthermore, the risk for family history of kidney disease was noticeable in the non-consanguineous population and significantly higher among the consanguineous patients (12% versus 18%, P<0.04). Consanguinity-associated kidney diseases affected all religious communities, in particular the Muslim and the Druze (36 and 39%), respectively versus 17% of the Christian community. Certain geographical areas were more involved than others such as the North, South and the Bekaa with the highest percentage (40%) in the latter. Socio-economical level was not a contributing factor. We conclude that the documentation of the underlying etiology in end-stage renal diseases (ESRD) seems to be deficient. Furthermore, consanguinity is prevalent in the Lebanese dialysis patients population, in particular the Muslim and the Druze communities. Consanguinity-associated kidney diseases pattern seems to differ from that of the general HD population by disease diagnosis and initiation at a younger age and a significantly higher risk for familial renal disease. It is a cultural phenomenon prevalent predominantly in the rural areas. We recommend a multi-approach including educational, informative and probably legislative strategy in order to limit and hopefully discourage consanguineous marriages.     

Effects of indomethacin on renal hemodynamics and on water and sodium excretion by the isolated dog kidney

Summary Blood-perfused isolated dog kidneys demonstrate steady increases in blood flow and in water and sodium excretion which could be attributed to the accumulation of renal prostaglandins in the perfusing blood. This hypothesis was tested by adding indomethacin, a potent inhibitor of prostaglandins synthesis, to the perfusing blood.Indomethacin completely prevented the vasodilation observed in control kidneys, without affecting glomerular filtration rate. Urine volume was not modified but sodium excretion was enhanced while the steady free water clearance increment observed in the control kidneys was depressed by indomethacin. The sum of sodium and free water clearances which, in the absence of antidiuretic hormone, constitutes an index of the part of the filtered load of solutes which escapes proximal tubular reabsorption, was not modified by indomethacin. Finally, indomethacin partially maintained the osmotic cortico-papillary gradient which was abolished after 2 hrs perfusion in control kidneys.These data suggest that prostaglandins accumulation in the blood is probably the major cause of the vasodilation taking place in isolated blood-perfused kidneys. This vasodilation does not account for decreased proximal reabsorption but partially explains the ADH-resistant diabetes insipidus developing in the isolated kidney. Moreover, indomethacin inhibits sodium reabsorption in the ascending limb of Henle's loop and increases water transport in the collecting duct.     

大鼠成体骨髓干细胞在肾小管上皮细胞再生中的作用

目的：观察肾小管上皮细胞的更新、再生有无来源于骨髓干细胞。方法:建立性别不匹配大鼠间的骨髓移植和肾脏移植模型，通过激光切割技术，将肾小管上皮细胞切割下来，提取其基因组DNA，用针对大鼠Y染色体上性别决定基因（Sry基因）的引物进行PCR反应，以观察提取的DNA中有无Sry基因。结果:据PCR反应结果，在2种模型所取标本的肾小管上皮细胞中，大部分可见Sry基因的存在。结论:骨髓干细胞可能是肾小管上皮细胞再生的一个来源。     

Cell culture from rat renal glomeruli

The primary culture of rat renal glomeruli was found to result in the ready outgrowth of two cells types. One type designated c-cells were cytokeratin positive and exhibited microvilli and cilia. The second type designated f-cells were vimentin positive and showed rugose surfaces. C-cells were polygonal in culture on plastic surfaces and were derived from cells of parietal epithelial origin. F-cells assumed a more extended form on plastic and were judged to be a sub-set of parietal epithelial cells. Neither cell type was derived from the visceral epithelium which was found to have been destroyed during isolation of the glomeruli. When cultured on isolated glomerular basement membrane both the c-cells and f-cells assumed a polygonal morphology but when grown on Matrigel the cells assumed the form of long strands interconnecting the outgrowths between the glomeruli. The appearance of the cells in the strands, judged from scanning electron microscopy, suggested that these were formed from f-cells but other cell types were entrained in the structures. Glomeruli subjected to vigorous proteinase digestion of the basement membrane allowed culture of a wider variety of cells. These included endothelial cells, judged by OX-43 antibody and anti-von Willebrand Factor staining, and mesangial cells. In cultures from glomeruli polygonal cells are often assumed to be visceral epithelial cells, the results from this study indicate that this assumption is unsound. The very different behaviour of cells grown on isolated basement membrane as compared with cells grown on Matrigel suggests that Matrigel may not faithfully mimic basement membrane with respect to cell response in culture.     

Long-term elevations of dietary sodium produce parallel increases in the renal excretion of urodilatin and sodium

The effects of dietary sodium intake on the renal excretion of urodilatin and of sodium were examined in six healthy male subjects. The 24-day study period was divided into three phases of 8 days each. Subjects Ingested 2.8 mequiv sodium (kg body weight)^–1 day^–1 during the first phase, 5.6 mequiv (kg body weight)^–1 day^–1 during the second phase, and 8.4 mequiv (kg body weight)^–1 day^–1 during the third phase. The excretion of both sodium (P<0.002) and urodilatin (P<0.006) increased in response to the increasing dietary sodium, while urine flow did not change. Urinary urodilatin excretion correlated closely with renal sodium excretion (P<0.001). Serum aldosterone levels (P<0.01) as well as serum renin levels (P<0.05) significantly decreased with increasing sodium intake. Plasma [Arg]vasopressin levels increased significantly (P<0.05). Plasma atrial natriuretic factor and cGMP levels as well as urinary cGMP excretion rates were unaltered by the changes in sodium intake. We conclude from these results that the renal natriuretic peptide, urodilatin, but not the main cardiac member of the natriuretic peptide family may be involved in the regulation of day-to-day sodium balance.     

Phosphate transport by rat renal brush border membrane vesicles: Influence of dietary phosphate,thyroparathyroidectomy, and 1,25-dihydroxyvitamin D3

In the present work we have investigated whether the changes in the renal handling of inorganic phosphate (Pi) induced by 1) dietary Pi, 2) removal of parathyroid glands and 3) 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], are associated with alterations in the Na-dependent Pi uptake by brush border membrane vesicles (BBMV) isolated from renal cortex. Shamoperated (SHAM) or thyroparathyroidectomized (TPTX) rats treated or not with 26 pmol/day of 1,25 (OH)₂D₃i.p. were fed low (0.2%) or high (1.2%)P diet for 7 days. The results showed that in SHAM, TPTX and TPTX+1,25 (OH)₂D₃ the Pi uptake by BBMV was greater after low than high Pi diet. It was greater in TPTX than in SHAM counterparts fed either diets. In TPTX fed low or high Pi diet 1,25 (OH)₂D₃ decreased the Pi uptake to the level observed in SHAM. A striking parallelism was found between variations in Pi uptake by BBMV and in the tubular Pi reabsorption of the whole kidney. The Na-dependent glucose, the mannitol uptake by BBMV, and the alkaline phosphatase activity in cortical homogenates and BBMV were not affected by the various treatments. Thus, dietary Pi, chronic TPTX and 1,25 (OH)₂D₃ appear to specifically affect the Na-dependent Pi transport system bound to the brush border membranes of renal cortical tubules. The alterations observed at this membrane level could account, at least in part, for the changes induced by these three factors on the overall tubular reabsorption of Pi.     

肾脏微血管内的压力分布与ANP的作用

本实验在40只大鼠经伺服零测压技术测定的肾脏微血管内压力分布及其ANP的作用均随血管树各段的口径变化而改变。分析小球前各段血管的压力降所占动脉总压降的比例得知:小叶间动脉占总压降的88％。肾小球毛细血管和出球小动脉亦具有较大的压力降。正常对照情况下,肾小球前血管内的压力分布与内径呈直线相关(r=0.869,n=65,P<0.01),其回归方程为平均压()=34.71±0.798×血管内径(D)。给ANP后肾小球前血管内的压力与内径仍呈直线相关(r=0.931,P<0.01),回归方程式为()=38.53+0.765D,其曲线右上移。本文结果提示,肾小球前微血管内压力分布与血管内径密切相关。小叶间动脉的阻力较大。     

Immunohistochemical detection of Fas and Fas ligand in sarcomatoid renal cell carcinoma

Sarcomatoid renal cell carcinomas (SRC) are rare neoplasms associated with a very poor prognosis. The aim of this study was to evaluate biomarker expression and clinical significance in this uncommon renal cancer. Cytokeratin, epithelial membrane antigen, vimentin, desmin, smooth muscle actin, CD34, S-100 protein, MIB 1, p53, Fas and Fas ligand immunohistochemical expression was investigated in seven renal cell carcinomas with sarcomatoid changes. No significant difference between sarcomatoid and nonsarcomatoid areas was observed with the different biomarkers, excepted for Fas ligand. Fas expression was diffuse in sarcomatoid and nonsarcomatoid areas. However, Fas ligand had a higher expression in sarcomatoid in comparison to nonsarcomatoid areas. Our results showed that Fas and Fas ligand are both expressed in renal cancer. We suggest that the aggressive behavior of sarcomatoid carcinoma may be related to a higher expression of Fas ligand by tumor sarcomatoid cells. These findings may indicate that Fas ligand is a possible therapeutic molecular target for treatment of SRC.