肾小球系膜增生机制的免疫组化研究

以单抗Ｍａｃ３８７作为单核细胞或中性粒细胞标志，以增殖细胞核抗原（ＰＣＮＡ）单抗作为细胞增殖指标，应用ＡＢＣ免疫酶标法对８７例各型肾小球肾炎肾穿刺组织进行了免疫组化研究，结果发现肾小球Ｍａｃ３８７阳性细胞数除紫癜性肾炎外，各型增生性肾炎显著高于非增生性肾炎（Ｐ〈０．０５）；ＰＣＮＡ阳性细胞数除ＩｇＡ肾炎外，各型增生性肾炎也均显著高于非增生性肾炎组（Ｐ〈０．０５）；肾小球Ｍａｃ３８７和ＰＣＮＡ阳性细     

血浆内皮素与肾小球疾病发病关系的探讨

血浆内皮素与肾小球疾病发病关系的探讨俞蔼，金小丽，游欢庆ＴＨＥＲＥＬＡＴｌＯＮＳＨＩＰＢＥＴＷＥＥＮＢＬＯＯＤＰＬＡＳＭＡＥＮＤＯＴＨＥＬＩＮＡＮＤＧＬＯＭＥＲＵＬＡＲＮＥＰＨＲＯＴＩＣＤＩＳＥＡＳＥＳ￥ＹｕＡｉ；ＪｉｎＸｉａｏｌｉ；ＹｏｕＨｕａｎｑ...     

THE “FIXED” CHARGE OF GLOMERULAR CAPILLARY WALL AS DETERMINANT OF PERMSELECTIVITY

The determinants of glomerular capillary wall (GCW) permeability to proteins have been subject of controversial discussion. To study this question we have developed a modified isolated perfused rat kidney model in which tubular transport processes are completely blocked by perfusion fixation with glutaraldehyde. This model allows to directly titrate the charge density of the GCW using albumin solutions buffered over a wide pH-range, a manipulation that cannot be performed in the intact kidney. Analyzing the results of these experiments helped to determine a fixed charge density of the GCW of 43mEq/L. In the present work, we used the isolated perfused fixed rat kidney model to study the influence of this fixed charge on the transglomerular passage of proteins. To do this, the fixed kidney was perfused with albumin solutions containing different isoforms of horseradish peroxidase. The lowest sieving coefficient was obtained with the acidic isoform (0.035±0.008, n=7), while the isoforms at pI 6.85 and 8.45 showed higher sieving coefficients (0.059±0.008, n=7 and 0.090±0.008, n=4, respectively). The highest sieving coefficient (0.59±0.031, n=6) was observed in perfusion experiments of the fixed kidney with cationic HRP (pI≥9.30). However, when comparing the sieving coefficients, the highly cationic isoform was excluded because it has a lower molecular weight than the other isoforms. The sieving coefficients of the other isoforms were significantly different (p < 0.05, ANOVA, Scheffé test). In conclusion, the presence of a discrete (even if lower than previously thought) “fixed” charge on the GCW of 43 mEq/L restricts the transglomerular passage of isoforms of horseradish peroxidase by a factor 2–3. These results imply that the influence of charge selectivity has been overstated in the literature.     

GLOMERULAR CAPILLARY GROWTH AND CELLULAR HYPERPLASIA IN A MODEL OF FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS

Background Mice with constitutive transgenic (tg) expression of interleukin‐4 (IL‐4) develop autoimmune‐type disorders resembling lupus nephritis. The kidneys show progressive glomerulosclerosis with immunoglobulin (Ig) and complement deposition. Methods This study investigated the role of renal IL‐4 expression and the relevance of glomerular Ig deposition in the pathogenesis of glomerulosclerosis in IL‐4tg mice. The mice were treated with either IL‐4 neutralizing antibody or the glucocorticoid methylprednisolone (MP). To further clarify whether the renal lesions were exclusively immune‐mediated, IL‐4tg mice were cross‐bred with δ chain deficient mice (δ MT^‐/‐), which are unable to produce Igs. Results Glomeruli of anti‐IL‐4‐treated tg mice showed a normal structure with negligible Ig deposits. Similarly, in MP‐treated tg mice only trace amounts of glomerular Ig deposits could be detected, although in comparison with wt mice, increased mesangial collagen deposition was evident. Despite complete absence of renal Ig deposits, IL‐4tg/δMT^‐/‐ mice developed progressive glomerulosclerosis with mesangial accumulation of collagen types I, IV and V. Renal IL‐4 expression was observed in both anti‐IL‐4‐ and MP‐treated IL‐4 tg mice, as well as in IL‐4tg/δMT^‐/‐ mice. There was no statistically significant difference in the number of glomerular T cells and macrophages between the groups. Conclusions Our data demonstrate that in this model glomerulosclerosis developed independently of and prior to Ig deposition, and imply that the initial accumulation of glomerular extracellular matrix was due to renal IL‐4 expression.     

B超对小儿非肾小球性血尿与胡桃夹现象的探讨

为了解我国儿童非肾小球性血尿中胡桃夹现象的发生率及其临床特点，对我院１９９１年初至１９９３年初２年内非肾小球性血尿患者进行了腹部Ｂ超检查，结果５２例中胡桃夹现象发生率为３６．５％，其中９／１９例表现为单纯血尿，１０／１９例表现为血尿伴蛋白尿，为血尿的病因诊断提供了新的线索。     

THE RETURN OF GLOMERULAR FILTERED ALBUMIN TO THE RAT RENAL VEIN – THE ALBUMIN RETRIEVAL PATHWAY

Background. Recent studies have demonstrated that the normal glomerular capillary wall (GCW) is not charge selective to albumin. This means that albumin flux across the GCW is high. This has been confirmed in studies where albumin uptake by the tubules has been inhibited. Therefore, there must be a high capacity postglomerular retrieval pathway in normal kidneys that returns filtered albumin back to the blood supply. Methods. This study identifies the presence of glomerular filtered albumin in the renal vein from the analysis of the decrease of radioactivity in the venous effluent after the injection of a pulse of tritium labeled albumin into the renal artery in vivo and in the isolated perfused kidney (IPK). Results. The glomerular filtered albumin is returned to the blood supply by a high capacity pathway that transports this albumin at a rate of 1830 ± 292 μg/min rat kidney (n = 14) (mean ± SEM). This pathway has been identified under physiological conditions in vivo and in the IPK. The pathway is specific for albumin as it does not occur for horseradish peroxidase (HRP). The pathway is inhibited in a non-filtering kidney. The pathway is also inhibited by NH₄Cl, an inhibitor of protein uptake. Conclusions. The high capacity retrieval pathway for albumin is most likely associated with transtubular cell transport. It is also apparent that most albuminuric states could be accounted for by the malfunctioning of this pathway without resorting to any change in glomerular permselectivity.