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1.
The platelet-derived growth factor (PDGF) antagonist, trapidil, which also blocks the thromboxane and/or PG-endoperoxide receptor and is an inhibitor of thromboxane synthetase, was administered during rabbit accelerated nephrotoxic nephritis; the clinical and histological evolution was studied as well as urinary immunoreactive thromboxane (i-TXB2) and immunoreactive prostaglandin E2 (i-PGE2) excretion. Although the dose we used has been shown to be effective in vivo, and it inhibited the urinary i-TXB2 excretion on days 5 and 10, it neither inhibited the enhanced production of i-TXB2 on day 1, nor prevented the glomerular influx of monocytes on days 5 and 10. All clinical and histological data tend to be worse rather than better in trapidil-treated animals on days 5 and 10. 相似文献
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R C Wiggins 《Laboratory investigation; a journal of technical methods and pathology》1985,53(3):335-348
This study was performed to investigate whether the Hageman factor (HF) system might contribute to glomerular damage in vivo. HF was purified from rabbit plasma. The proteolytic activation pattern of 80,000-dalton rabbit HF was the same as that previously reported for human HF. Anti-HF IgG, raised in a goat, was monospecific as judged by immunodiffusion analysis and inhibited HF activity in rabbit plasma. A telescoped model of nephrotoxic nephritis in the rabbit was developed using guinea pig antirabbit glomerular basement membrane IgG injected into rabbits preimmunized against guinea pig IgG. In this model protein excretion was increased by days 3 to 4 in association with glomerular influx of acute inflammatory cells. By days 5 and 6 fibrin was present within glomerular capillaries, beneath endothelial cells, in Bowman's space, and in proximal tubules. By fluorescent microscopic analysis rabbit IgG and C3 had accumulated along the glomerular capillary wall; however, no HF was detectable in glomerular capillary wall over the initial 10 days of glomerular injury. Positive fluorescence for HF was seen within Bowman's space and in tubules along with albumin and plasmin- and fibrin-related antigens. Although the circulating antigenic HF concentration did not change during the glomerular injury, the rate of turnover of 125I-HF did increase. However, when this was factored for turnover of 131I-albumin in a paired study, the relative turnover of 131I-albumin was found to be faster than that of 125I-HF. Proteolysis of 125I-HF in plasma consistent with HF activation was noted in only one of these rabbits in spite of a decrease in antigenic C3 level to 54% of baseline. The 125I-HF appearing in urine of nephritic rabbits had undergone proteolysis from the native 80,000-dalton parent molecule to form fragments of 50,000 and 30,000 daltons, compatible with HF activation. Urine from nephritic rabbits also contained procoagulant activity that was HF dependent. These results are compatible with the concept that HF passively crosses the damaged glomerular filter where it may become activated in Bowman's space or in fluid draining damaged glomeruli in this model of nephrotoxic nephritis in the rabbit. 相似文献
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Takashi Nose Kaito Tsurumi Kenji Kawada Hiroichi Nagai Hiroaki Yamada Ikuhisa Yakuo Akitsugu Ojima Akihide Koda 《Inflammation》1989,13(4):401-414
In order to characterize nephrotoxic serum nephritis accelerated with rabbit -globulin in mice, histopathological studies were carried out 15 days after NTS injection, the time when increases in urinary protein and serum cholesterol and a decrease in serum albumin were apparent. Characteristic changes were widespread thickening of glomerular capillary walls and widening of mesangial areas, owing to deposits of mesangial matrixlike substances. The mesangial interposition into subendothelial areas and the resultant narrowing of the capillary lumen were shown ultrastructurally. In severely affected glomeruli, a hyaline nodular lesion was observed. Visceral epithelial cells demonstrated fusion of the foot processes, microvilli formation, occasional proliferation, and enlargement. Parietal epithelial cells proliferated, forming a cellular crescent. Based on these characteristics, it appears this nephritic model shares a common pathology with human membranoproliterative glomerulonephritis type 1 and crescentic glomerulonephritis and can be considered an appropriate model for producing severe nephritis for short periods. 相似文献
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C Zoja D Corna D Macconi P Zilio T Bertani G Remuzzi 《Laboratory investigation; a journal of technical methods and pathology》1990,62(1):34-40
To study the efficacy of tissue plasminogen activator (PA) therapy to prevent deteriorating renal function in experimental proliferative glomerulonephritis we used a model of nephrotoxic nephritis induced in rabbits by injection of antiglomerular basement membrane antiserum. Saline or recombinant tissue plasminogen activator (rt-PA, 1.3 mg/kg body weight) was infused daily for 7 days starting from day 7 after the injection of antiglomerular basement membrane antiserum when the disease had been already triggered. Animals were killed on day 14. Rabbits given saline had abundant deposits of fibrin and crescents in about 67% of glomeruli. rt-PA significantly protected animals from glomerular fibrin deposition and crescent formation with respect to saline-treated animals. Renal function measured as creatinine clearance was dramatically impaired in rabbits given saline. Treatment with rt-PA ameliorated the renal function impairment of nephrotoxic nephritis. rt-PA did not produce a systemic fibrinolytic state as indicated by alpha 2-antiplasmin level measurement. These results suggest that tissue PA may have important implications in preventing renal function deterioration in humans with crescentic glomerulonephritis and fibrin depositions. 相似文献
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Origin of glomerular crescents in rabbit nephrotoxic nephritis 总被引:1,自引:0,他引:1
The origin of glomerular crescents was investigated in an accelerated model of rabbit nephrotoxic nephritis. In rabbits immunised against sheep gamma-globulin, the administration of sheep nephrotoxic serum provoked cellular crescent formation affecting 30 to 90 per cent. of glomeruli at 6 days. The crescents were composed predominantly of cells with ultrastructural features of macrophages. In animals depleted of circulating leukocytes by whole body irradiation, with or without shielding of the kidney, crescent formation was inhibited despite severe glomerular damage and fibrin deposition in Bowman's space. These findings support the hypothesis that glomerular crescents develop principally from the emigration and accumulation of bone marrow-derived mononuclear cells. 相似文献
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The origin of glomerular crescents in experimental nephrotoxic serum nephritis in the rabbit. 总被引:10,自引:0,他引:10
V Cattell S W Jamieson 《Laboratory investigation; a journal of technical methods and pathology》1978,39(6):584-590
The origin of glomerular crescents and diffuse hypercellularity was investigated in rabbits receiving a single intravenous injection of nephrotoxic serum. Experiments to demonstrate local glomerular proliferation included mitotic counting at intervals after nephrotoxic serum and autoradiography of kidneys 1 hour after pulse-tritiated thymidine labeling. There was an increase in local endocapillary proliferation between days 4 and 6 when severe diffuse hypercellularity developed. From days 8 to 13 during crescent formation there was considerable local epithelial proliferation. To assess the role of infiltrating bone marrow cells a new technique of renal transplantation in rabbits was developed. Kidneys from unlabeled donors were transplanted on either day 4 or day 9 into recipients prelabeled with tritiated thymidine, and labeled cells were sought in glomeruli of transplants 1 to 4 days later. Large numbers of labeled cells appeared on days 5 to 6 in areas of endocapillary hypercellularity in glomeruli of animals given transplants on day 4 indicating a significant influx of bone marrow cells. In contrast, in kidneys transplanted on day 9, few labeled cells were present in crescents on days 10 to 11. Autoradiographic labeling of mononuclear phagocytes in carrageenan granulomas and interstitial renal infiltrates in recipients were used as positive controls of bone marrow cell labeling. We conclude that in the early phase of diffuse hypercellularity there is considerable blood monocyte infiltration, whereas crescents which develop later are principally the result of glomerular epithelial cell proliferation. 相似文献
7.
K. V. Opalenov O. P. Gladskikh E. M. Pal'tseva A. A. Ivanov 《Bulletin of experimental biology and medicine》1998,126(1):737-739
The modeling of rat nephrotoxic nephritis showed that the development of matrixassociated forms of basic fibroblast growth
factor and transforming growth factor-β1 can be one of the mechanisms regulating their activity. Disturbances in the development
of these associated complexes may result in glomerulosclerosis.
Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 7, pp. 107–109, July, 1998 相似文献
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用免疫细胞化学方法研究了大鼠肾毒血清肾炎(nephrotoixcnephritis,NIN)发病头7天肾组织中血小板衍生的生长因子(platelet-derivedgrowthfactor,PDGF)增生细胞核抗原(proliferatincellnuclearanigen,PCNA)和单核/巨噬细胞的变化以及检测这些细胞之间及其与肾功能之间的相关性。结果表明,NTN大鼠发病第1天,肾小球内未能检 相似文献
10.
吴升华 《中国病理生理杂志》1999,15(12):1087-1089
目的:了解肾炎模型中肾小球血栓素(TX)A2受体的变化并探讨其机制。方法:建立大鼠加速性肾毒性血清性肾炎模型。应用放免法测定肾小球产生的TXB2,应用放射配体受体分析法及Western blot 分析法测定肾小球TXA2受体。结果:肾炎鼠肾小球产生的TXB2增多,肾小球TXA2受体的最大结合容量(Bmax)及受体蛋白量减少。应用TX A2合酶抑制剂furegrelate对肾炎鼠预处理,可抑制肾小球TXB2的升高,可使TXA 相似文献
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Both Fcgamma receptor I and Fcgamma receptor III mediate disease in accelerated nephrotoxic nephritis
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Tarzi RM Davies KA Claassens JW Verbeek JS Walport MJ Cook HT 《The American journal of pathology》2003,162(5):1677-1683
Recognition of immune complexes in glomeruli by activator Fcgamma receptors (FcgammaRI and FcgammaRIII) is an important step in the development of glomerulonephritis. The low-affinity receptor (FcgammaRIII) has previously been shown to be important in passive heterologous immune complex glomerulonephritis. However, most forms of human glomerulonephritis involve an active immune response, and the relative importance of FcgammaRI (high-affinity receptor) and FcgammaRIII in an active model of glomerulonephritis is not known. We have now studied accelerated nephrotoxic nephritis in FcgammaRIII-/- mice and FcgammaRI/III double-deficient mice, and compared them with matched wild-type controls and FcRgamma chain-deficient (FcRgamma-/-) mice. Mice were immunized against sheep IgG and injected with sheep anti-mouse glomerular basement membrane antibody 5 days later. Both FcgammaRI/III double-deficient mice and FcRgamma-/- mice were strongly protected from renal injury. In contrast, FcgammaRIII-/- mice developed substantial nephritis, although there was a dose-dependent partial protection from glomerular crescents and thrombosis. Despite this histological protection from injury, the macrophage infiltrate was not reduced, implying a dissociation of macrophage accumulation from activation in the absence of activatory FcgammaRIII. Therefore, both FcgammaRI and FcgammaRIII play a role in this active model of glomerulonephritis, because both had to be deficient to protect markedly from disease. 相似文献
14.
H. T. Cook M. M. Ruseva M. Szajna M. C. Pickering K. J. Woollard M. Botto 《Clinical and experimental immunology》2018,192(3):337-347
Hyperlipidaemia accompanies chronic renal disease either as a consequence of the renal dysfunction or as part of generalized metabolic derangements. Under both situations, the lipid profile is characterized by accumulation of triglyceride‐rich lipoproteins (TGRLs). This lipid profile is recognized as a risk factor for cardiovascular complications. Whether it may pose a risk for renal injury as well remains unclear. A hyper‐TGRL state was generated in C57BL/6 mice using poloxamer‐407 (P‐407) and immune complex‐mediated renal injury was triggered using the accelerated nephrotoxic nephritis (ANTN) model. The hyper‐TGRL animals were hypersensitive to ANTN demonstrated by greater haematuria and glomerular cellularity. These changes were accompanied by increased glomerular accumulation of CD68+ macrophages. The hypersensitive response to ANTN was not seen in low‐density lipoprotein receptor knock‐out mice fed with a high fat diet, where triglyceride levels were lower but cholesterol levels comparable to those obtained using P‐407. These data indicate that a hyper‐TGRL state might be more detrimental to the kidneys than low‐density lipoprotein‐driven hypercholesterolaemia during immune complex‐mediated nephritis. We speculate that the hyper‐TGRL environment primes the kidney to exacerbated renal damage following an inflammatory insult with increased accumulation of macrophages that may play a key role in mediating the injurious effects. 相似文献
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Decay-accelerating factor confers protection against complement-mediated podocyte injury in acute nephrotoxic nephritis 总被引:8,自引:0,他引:8
Lin F Emancipator SN Salant DJ Medof ME 《Laboratory investigation; a journal of technical methods and pathology》2002,82(5):563-569
SUMMARY: Decay-accelerating factor (DAF or CD55) is one of a set of regulators that function to protect self cells from deposition of autologous C3b on their surfaces. Its relative importance in vivo, however, is incompletely understood. As one approach to address this issue, we induced nephrotoxic serum (NTS) nephritis in wild-type mice and Daf1 gene-floxed mice devoid of renal DAF expression. For these experiments NTS IgG was administered at a dose (0.5 mg iv) that requires complement for glomerular injury. After 18 hours, renal injury was assessed by proteinuria and by histologic, immunohistochemical, and electron microscopic analyses of kidneys. Fifteen normal and 15 DAF-deficient mice were studied. Baseline albuminuria in the Daf1(-/-) mice was 115.9 +/- 41.4 microg/mg creatinine as compared with 85.7 +/- 32.3 microg/mg creatinine in their Daf1(+/+) littermates (p = 0.075). After administration of NTS IgG, albuminuria increased to 2001.7 +/- 688.7 microg/mg creatinine as compared with 799.7 +/- 340.5 microg/mg creatinine in the controls (p = 0.0003). Glomerular histology was similar in Daf1(-/-) and Daf1(+/+) mice, with essentially no infiltrating leukocytes. In contrast, electron microscopy revealed severe podocyte fusion in the Daf1(-/-) mice but only mild focal changes in the controls. Immunohistochemical staining showed equivalent deposition of the administered (sheep) NTS IgG in the Daf1(-/-) and Daf1(+/+) animals. This contrasted with marked deposition of autologous murine C3 in the former and minimal deposition in the latter. The results show that DAF is essential physiologically for protecting glomeruli against autologous complement attack initiated by the classical pathway. 相似文献
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Vascular endothelial growth factor, platelet-derived growth factor, and insulin-like growth factor-1 promote rat aortic angiogenesis in vitro. 总被引:10,自引:2,他引:10
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The purpose of this study was to evaluate the vasoformative response of isolated vascular explants to a variety of growth factors that have been shown to stimulate angiogenesis. Rings of rat aorta were cultured in collagen gels under serum-free conditions in the presence or absence of vascular endothelial growth factor (VEGF), natural platelet-derived growth factor (PDGF), PDGF-AA, PDGF-BB, insulin-like growth factor-1 (IGF-1), transforming growth factor-alpha (TGF-alpha), transforming growth factor-beta 1 (TGF-beta 1), epidermal growth factor (EGF), interleukin-1 alpha (IL-1 alpha), or hepatocyte growth factor (HGF). The angiogenic response of the rat aorta was stimulated by VEGF, PDGF, PDGF-AA, PDGF-BB, and IGF-1. Maximum stimulatory effects were obtained with VEGF and PDGF-BB. By contrast, TGF-beta 1 and IL-1 alpha had inhibitory activity. No significant effects were observed with TGF-alpha, EGF, or HGF. The vascular outgrowth of VEGF-stimulated cultures was primarily composed of microvessels, whereas that of PDGF- and IGF-1-stimulated cultures contained an increased number of fibroblast-like cells. The inability of TGF-alpha, TGF-beta 1, IL-1 alpha, EGF, and HGF to stimulate rat aortic angiogenesis in serum-free culture suggests that either these factors require the mediatory activity of accessory cells that are not present in the rat aorta model or that blood vessels are heterogeneous in their capacity to respond to different angiogenic factors. 相似文献
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A quantitative evaluation of anticoagulants in experimental nephrotoxic nephritis. 总被引:4,自引:0,他引:4
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The protective effects of anticoagulants in nephrotoxic nephritis in rabbits have been studied, using various doses of heparin and defibrination with ancrod. Massive doses of heparin (2000 units/kg/day) were required before significant reduction in glomerular fibrin deposition, extracepillary cell proliferation and urea retention occurred. Doses of 300 and 1000 units/kg/day were insufficient to modify fibrin deposition and cell proliferation. Defibrination with ancrod provided protection, judged by histological and functional criteria, comparable to 2000 units of heparin/kg/day; but fibrin could still be demonstrated in the glomeruli of animals treated with 2000 units of heparin/kg/day, contrasting with the virtual absence of fibrin in animals given ancrod. 相似文献
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M K Bach J R Brashler B K Stout H G Johnson M E Sanders A H Lin R R Gorman M J Bienkowski T Ishizaka 《International archives of allergy and immunology》1992,97(2):121-129
Activated eosinophils are believed to be major contributors to the chronic inflammatory sequelae of asthma, but the details of the mechanism of eosinophil activation in vivo are unknown. In our search for physiologically important modes of eosinophil activation, we studied the effects of recombinant human platelet-derived growth factor (PDGF) on human peripheral blood eosinophils. We compared two activation end-points: secretion of granule contents, exemplified by the release of eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN), and the generation of active oxygen metabolites (O2- production). PDGFc-sis dose dependently stimulated the secretion of large amounts of EPO and EDN from eosinophils. Higher concentrations of PDGF induced a dose-dependent O2- production, especially if the cells were first primed with low concentrations of phorbol ester. These activities were not seen with the AA homodimer of PDGF, suggesting that the activation was receptor dependent. However, several attempts to directly demonstrate the existence of such receptors were unsuccessful. The magnitude of the secretory response to PDGF, and the realization that eosinophils could be easily exposed to this substance as they travel towards the lung, suggests the possibility that this growth factor may be a physiologically important activator of eosinophils in the pulmonary inflammation which is associated with asthma. 相似文献