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硫酸肝素蛋白多糖 (HSPGs)是GBM中重要功能性组分 ,参与构成负电荷屏障。其结构紊乱和功能异常在许多蛋白尿性肾小球疾病进展中起关键作用。并参与病理情况下肾小球炎症 ,系膜细胞增殖和系膜扩张过程。本文对HSPGs与肾小球疾病关系方面的研究进展作一综述 相似文献
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刘晶 《国际泌尿系统杂志》2010,30(5)
传统认为,肾小球肾炎(glomerulonephritis,GN)的发病机制与肾小球原位免疫复合物形成或循环中免疫复合物沉积于肾脏,激活补体而引起的肾脏损伤等有关.近年研究发现,GN的发病机制,不仅与T、B淋巴细胞介导的适应性免疫有关,而且与中性粒细胞、肥大细胞、单核/巨噬细胞、树突状细胞(dendritic cell,DC)等免疫细胞介导的固有免疫密切相关.因此本文旨在对免疫失衡及其介导的炎症反应在原发性肾小球疾病中的作用机制作一综述. 相似文献
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原发性肾小球疾病诊治进展 总被引:3,自引:0,他引:3
原发性肾小球肾炎(PGN,primary glomerulonephritis)由于其病因未明,各病理类型之间症状相似以及发病机制的不明确,给诊断和治疗带来了很多不便,本文就原发性肾小球肾炎的诊断治疗方面作一综述,主要在于论述近年其诊断治疗方面的一些进展。 相似文献
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肝素疗法对肾小球肾炎患者血小板活化状态的影响及其临床意义 总被引:6,自引:0,他引:6
我们对接受肝素疗法的肾小球肾炎患者外周血小板计数(PC)、体积(PV)、分布宽度(PDW)、血小板表面CD62P(血小板P选择素)、CD63(血小板活化因子)和CD41(纤维蛋白受体)表达水平进行测定,探讨肝素疗法对不同病理类型肾炎患者血小板活化状态的影响及其临床意义。一、对象与方法1.对象:选择处于高凝状态的表现为肾病综合征的肾小球肾炎患者95例,男56例,女39例,年龄8~13岁。根据病理类型将治疗对象分为微小病变组(MC组)10例,肾小球硬化组(GS组)30例,膜性肾病组(MN组)20例,… 相似文献
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杨小燕 《国外医学:泌尿系统分册》1996,16(4):164-167
丙型肝炎病毒感染在引起肝脏病变的同时存在肾小球的病变,本文综述HCV的特征,HCV感染与肾小球病变、与肾小球肾炎相关机理,以及肾小球疾病HCV的检测方法,HCV与肾小球疾病相关的治疗。 相似文献
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杨小燕 《国际泌尿系统杂志》1996,(4)
丙型肝炎病毒(HCV)感染在引起肝脏病变的同时存在肾小球的病变。本文综述了HCV的特征,HCV感染与肾小球病变、与肾小球肾炎相关机理,以及肾小球疾病HCV的检测方法,HCV与肾小球疾病相关的治疗。 相似文献
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RAGE是多配体的细胞表面受体之一,可传导AGEs信号、介导并放大细胞对AGEs的大部分应答反应。在疾病状态下,RAGE与配体结合后通过上调其自身表达放大了配体的信号,通过ROS-Ras-MAPK-NF-κB.Cdo42-RAC和JAK-STAT信号途径产生多种生物学效应。 相似文献
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Recent studies, including those by van den Hoven and colleagues, have challenged the classic negative-charge theory of glomerular filtration. However, the possibility remains that heparan sulfate in the glomerular basement membrane plays a role in maintaining the glomerular filtration barrier. 相似文献
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The glomerular capillary wall functions as both a size-selective and charge-selective barrier. Heparan sulfate is known to be an important component of the charge-selective barrier to filtration of polyanions. We studied the alterations in both the charge and size selectivity barriers in a model of experimental membranous nephropathy in the rabbit. The fractional clearance of both charged and uncharged dextrans compared to inulin was measured. Sulfate incorporation into glycosaminoglycans was measured and the glomerular heparan sulfate was isolated and biochemically characterized. Membranous nephropathy in the rabbit was induced with daily injections of cationic bovine serum albumin. After three weeks of injection animals had 735 +/- 196 mg/24 hours of protein excretion. There was no change in [35S] incorporation in 24 hours by experimental animals, 440 +/- 91 DPM/mg dry weight of glomeruli, N = 9 versus 410 +/- 98, N = 11 in controls. The percentage of [35S] incorporated into heparan sulfate versus chondroitin sulfate was decreased, 60% +/- 3 versus 79% +/- 2, P less than 0.001. Heparan sulfate from membranous nephropathy eluted from ion exchange chromatography in a lower molarity salt, indicating a lower effective charge. Fractional clearance of neutral dextrans was significantly increased in membranous nephropathy for dextrans greater than 48 A, while fractional clearance of dextran sulfates was significantly increased compared to controls for dextrans greater than 32 A. Thus, in membranous nephropathy there is loss of both charge selectivity and size selectivity. The loss of charge selectivity correlated with a change in the structure of the glomerular heparan sulfate.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Wijnhoven TJ Lensen JF Wismans RG Lefeber DJ Rops AL van der Vlag J Berden JH van den Heuvel LP van Kuppevelt TH 《Journal of the American Society of Nephrology : JASN》2007,18(12):3119-3127
Heparan sulfate (HS) within the glomerular basement membrane (GBM) is thought to play a major role in the charge-selective properties of the glomerular capillary wall. Recent data, however, raise questions regarding the direct role of HS in glomerular filtration. For example, in situ studies suggest that HS may prevent plasma macromolecules from clogging the GBM, keeping it in an "open" state. We evaluated this potential role of HS in vivo by studying the passage of protein through the glomerular capillary wall in the presence and absence of HS. Intravenous administration of neuraminidase removed neuraminic acid--but not HS--from the GBM, and this led to albuminuria. Concomitant removal of HS with heparinase III, confirmed by ultrastructural imaging, prevented the development of albuminuria in response to neuraminidase treatment. Taken together, these results suggest that HS keeps the GBM in an open state, facilitating passage of proteins through the glomerular capillary wall. 相似文献
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Interleukin-8 alters glomerular heparan sulfate glycosaminoglycan chain size and charge in rats 总被引:3,自引:0,他引:3
We have previously shown that the in vivo infusion of interleukin-8 (IL8) in rats causes albuminuria and an increased catabolism
of the heparan sulfate (HS) glycosaminoglycans (GAG). The purpose of this study was to characterize further the in vivo effect
of IL8 on rat HSGAG. The left renal artery of male rats was continuously infused with IL8 (750 ng/ml, 4 rats) or 1% bovine
serum albumin (3 rats) using an osmotic pump. On the 5th day of infusion, 35sulfate (1.0 mCi/100 g) was given intraperitoneally and the rat was killed 8 h later. Glomerular HSGAG was isolated and its
size and charge was determined by liquid chromatography. The HSGAG 35sulfate uptake was higher in IL8-treated rats than controls (387±138 vs. 246±15 cpm/1,000 glomeruli, mean ± SD, P<0.05). No differences in HSGAG size were observed between IL8-treated and control animals. However, after ion exchange chromatography,
there was a shift to the left in the elution profile of IL8-treated rats, demonstrating the presence of chains with decreased
negative charge. IL8 infusion into rats results in a decreased total negative charge of the HSGAG. Because IL8 has been found
in the serum of some patients with minimal lesion nephrotic syndrome, this finding may explain, at least in part, the reported
reduced glomerular charge barrier observed in these patients.
Received: 10 November 1998 / Revised: 8 June 1999 / Accepted: 8 June 1999 相似文献
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In vitro decrease of glomerular heparan sulfate by lymphocytes from idiopathic nephrotic syndrome patients 总被引:4,自引:0,他引:4
BACKGROUND: Lymphocytes are involved in the physiopathologic mechanism of idiopathic nephrotic syndrome (INS). We have recently demonstrated that plasma from patients with INS decreases human glomerular epithelial cell (GEC) glycosaminoglycans (GAGs), particularly heparan sulfates (HS) in vitro. In this study we investigate the effect of peripheral blood lymphocytes (PBL) from INS patients on glomerular cell GAG and HS. METHODS: Human GECs were cultured with total peripheral blood mononuclear cells (PBMCs), PBL, and monocytes from patients and controls. The amounts of GAG and HS were assessed using a cationic membrane after metabolic labeling. RESULTS: In coculture with GECs, mononuclear cells from controls decreased total epithelial cell GAG (-30% with PBMC, P < 0.05; -25% with PBL, P < 0.02; -19% with monocytes, P < 0.05). Particularly HSs were decreased (-36% with PBMC, P < 0.05; -27% with PBL, P < 0.02; and -19% with monocytes, P < 0.05). When GECs were in coculture with PBL from INS patients, the decrease in GAG and HS was significantly greater in comparison to control PBL (-10%, P < 0.02; -10%, P < 0.02, respectively, for GAG and HS). Moreover, supernatants of stimulated PBMCs from patients decreased also GAG and HS in comparison with controls (-13%, P < 0.02; -15%, P < 0.02, respectively, for GAG and HS). CONCLUSION: These data provide direct evidence that PBLs from INS patients are able to decrease GEC HS as previously shown with plasma from patients. This might be instrumental in the onset of albuminuria. 相似文献
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C J Raats M E Luca M A Bakker A Van Der Wal P Heeringa H Van Goor J Van Den Born E De Heer J H Berden 《Journal of the American Society of Nephrology : JASN》1999,10(8):1689-1699
In a time-study of active Heymann nephritis, the expression of agrin, the main heparan sulfate proteoglycan in the glomerular basement membrane, was analyzed in relation to deposition of IgG and complement in the glomerular capillary wall and the development of albuminuria. Binding of IgG autoantibodies to the glomerular capillary wall could be detected from 2 wk onward, followed by activation of complement after 6 wk. Progressive albuminuria developed from 6 wk onward to a level of 274+/-68 mg/18 h at week 12. The staining intensity for the agrin core protein decreased slightly, and the staining intensity for the heparan sulfate stubs that were still attached to the core protein after heparitinase digestion remained normal. From week 6 onward, however, a progressive decrease was seen in the staining of two monoclonal antibodies (mAb) directed against different epitopes on the heparan sulfate polysaccharide side chain of agrin (to 35 and 30% of the control level, respectively, at week 12, both mAb P = 0.016). Moreover, albuminuria was inversely correlated with heparan sulfate staining as revealed by these antibodies (r(s) = -0.82 and r(s) = -0.75, respectively, both mAb P < 0.0001). This decrease in heparan sulfate staining was due to a progressive reduction of glomerular heparan sulfate content to 46 and 32% of control level at week 10 and week 12 of the disease, respectively, as measured biochemically. It is speculated that the observed decrease in glomerular heparan sulfate in active Heymann nephritis is due to complement-mediated cleavage of heparan sulfate, resulting in an increased permeability of the glomerular basement membrane to macromolecules. 相似文献
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Undersulfation of glomerular basement membrane heparan sulfate in experimental diabetes and lack of correction with aldose reductase inhibition 总被引:2,自引:0,他引:2
In this study we examined the effect of experimental diabetes and of treatment with an aldose reductase inhibitor on the level of sulfation of glomerular basement membrane (GBM) heparan sulfate, the principal glycosaminoglycan in this extracellular matrix. Glycosaminoglycans were isolated from GBM purified from control, streptozocin-induced diabetic, and sorbinil-treated diabetic rats and analyzed for sulfate and uronate content. Glomerular yields from diabetic kidneys were greater than those from control animals, but the amount of sulfate per glomerulus in diabetic samples, both untreated and sorbinil treated, did not differ significantly from that in control samples. However, the sulfate-to-uronate ratio in heparan sulfate isolated from diabetic GBM (0.34 +/- 0.08) was significantly less than in control samples (0.69 +/- 0.11), and treatment of diabetic rats with an aldose reductase inhibitor did not correct this reduced ratio (0.36 +/- 0.06). The results indicate that there is an undersulfation of heparan sulfate of GBM in experimental diabetes, an abnormality that may contribute to loss of anionic sites and decreased charge selectivity of the glomerular filtration barrier. The findings further suggest that this abnormality results from disturbances in glycosaminoglycan synthesis and/or metabolism in diabetes that are independent of polyol-pathway activation in the renal glomerulus. 相似文献
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Recent insights into the structure and functions of heparan sulfate proteoglycans in the human glomerular basement membrane. 总被引:7,自引:0,他引:7
A J Groffen J H Veerkamp L A Monnens L P van den Heuvel 《Nephrology, dialysis, transplantation》1999,14(9):2119-2129
As the first barrier to be crossed on the way to urinary space, the glomerular basement membrane (GBM) plays a key role in renal function. The permeability of the GBM for a given molecule is highly dependent on its size, shape and charge. As early as 1980, the charge-selective permeability was demonstrated to relate to the electrostatic properties of covalently bound heparan sulfates (HS) within the GBM. Since the identification of perlecan as a heparan sulfate proteoglycan (HSPG) of basement membranes, the hypothesis that perlecan could be a crucial determinant of GBM permselectivity received considerable attention. In addition to perlecan, the GBM also contains other HSPG species, one of which was identified as agrin. The high local expression of agrin in the GBM, together with the presence of agrin receptors at the cell matrix interface, suggests that this HSPG contributes to glomerular function in multiple ways. Here, we review the current knowledge regarding the structure and functions of HSPGs in the GBM, and discuss how these molecules could be involved in various glomerular diseases. Possible directions for future investigation are suggested. 相似文献
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ACE inhibition preserves heparan sulfate proteoglycans in the glomerular basement membrane of rats with established adriamycin nephropathy 总被引:2,自引:0,他引:2
Wapstra FH Navis GJ van Goor H van den Born J Berden JH de Jong PE de Zeeuw D 《Experimental nephrology》2001,9(1):21-27
The gradual onset of the antiproteinuric effects of ACE inhibition suggests that structural effects on the glomerular basement membrane (GBM) may be involved in their renoprotective action. To test this hypothesis, we studied the effects of lisinopril (5 mg/kg/24 h) on proteinuria, focal glomerulosclerosis (FGS) and glomerular heparan sulfate (HS) proteoglycan (HSPG) GBM staining in rats with established Adriamycin nephrosis. Treatment was started 6 weeks after disease induction. As expected, lisinopril reduced blood pressure, proteinuria and the FGS score. In control rats, Adriamycin nephrosis was associated with significantly impaired GBM staining for both HSPG core protein (assessed from BL-31 staining) and HS staining (assessed from JM-403 staining) 12 weeks after disease induction. In rats treated with lisinopril (5 mg/kg/24 h) GBM staining was significantly better preserved for HS as well as for HSPG core protein. These data suggest that structural effects on the GBM, improving glomerular permselectivity, may be involved in the renoprotective effects of ACE inhibition in proteinuria-induced renal damage. 相似文献