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用硫酸乙酰肝素免疫大鼠引发的肾损伤的特征

Characterization of renal injury initiated by immunization of rats with heparan sulfate.

作者信息

Abrass C K, Cohen A H

机构信息

Division of Nephrology, Veterans Administration Medical Center, Seattle, WA 98108.

出版信息

Am J Pathol. 1988 Jan;130(1):103-11.

PMID:2962503
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1880534/
Abstract

To investigate the role of antibody to heparan sulfate (HS) in the development of glomerular injury, male Lewis rats were immunized with HS and compared with unimmunized controls. In HS-immunized rats circulating antibodies that bound to renal basement membranes, an increase in serum creatinine (0.8 mg/dl versus 0.6 in controls P less than 0.01), and a 40% decline in creatinine clearance developed. In no animal did abnormal proteinuria develop. By histologic examination there was glomerular and interstitial capillary engorgement with erythrocytes, modest infiltration by polymorphonuclear leukocytes, and no proliferation of intrinsic glomerular cells. Immunofluorescence microscopy demonstrated deposits of rat IgG along the glomerular basement membrane. Bowman's capsule, and peritubular capillaries. Electron-microscopic examination revealed capillary engorgement with erythrocytes that appeared adherent to each other and contained entrapped areas of rarefied material. These observations demonstrate that binding of antibody to HS in the glomerulus induces a mild inflammatory reaction and a reduction in glomerular filtration rate, but no abnormal proteinuria.

摘要

为研究硫酸乙酰肝素(HS)抗体在肾小球损伤发展中的作用,将雄性Lewis大鼠用HS免疫,并与未免疫的对照大鼠进行比较。在HS免疫的大鼠中,出现了与肾基底膜结合的循环抗体,血清肌酐升高(0.8mg/dl,对照组为0.6mg/dl,P<0.01),肌酐清除率下降40%。没有一只动物出现异常蛋白尿。组织学检查显示肾小球和间质毛细血管红细胞充盈,多形核白细胞轻度浸润,肾小球固有细胞无增殖。免疫荧光显微镜检查显示大鼠IgG沿肾小球基底膜、鲍曼囊和肾小管周围毛细血管沉积。电子显微镜检查显示毛细血管红细胞充盈,红细胞相互粘连,含有稀疏物质的包埋区域。这些观察结果表明肾小球中抗体与HS的结合可诱导轻度炎症反应和肾小球滤过率降低,但无异常蛋白尿。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a84/1880534/0d71f7e9b32c/amjpathol00136-0118-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a84/1880534/0aa452eab474/amjpathol00136-0116-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a84/1880534/a2fed9eb0ed3/amjpathol00136-0117-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a84/1880534/ba212eb36792/amjpathol00136-0117-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a84/1880534/0d71f7e9b32c/amjpathol00136-0118-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a84/1880534/0aa452eab474/amjpathol00136-0116-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a84/1880534/a2fed9eb0ed3/amjpathol00136-0117-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a84/1880534/ba212eb36792/amjpathol00136-0117-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a84/1880534/0d71f7e9b32c/amjpathol00136-0118-a.jpg

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本文引用的文献

1
Localization of the nephrotoxic antigen within the isolated renal glomerulus.肾毒性抗原在分离出的肾肾小球内的定位。
AMA Arch Pathol. 1951 Jun;51(6):629-39.
2
EXPERIMENTAL GLOMERULONEPHRITIS. V. STUDIES ON THE INTERACTION OF NEPHROTOXIC ANTIBODIES WITH TISSUE OF THE RAT.实验性肾小球肾炎。V. 肾毒性抗体与大鼠组织相互作用的研究
J Exp Med. 1965 May 1;121(5):697-714. doi: 10.1084/jem.121.5.697.
3
A method for the separation of acid mucopolysaccharides: its application to the isolation of heparin from the skin of rats.一种酸性粘多糖的分离方法:其在从大鼠皮肤中分离肝素的应用。
J Biol Chem. 1961 Apr;236:983-7.
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Studies of biologic properties of proteoglycans from bovine aorta.牛主动脉蛋白聚糖生物学特性的研究。
Lab Invest. 1980 Feb;42(2):190-6.
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Altered glomerular permeability as a result of focal detachment of the visceral epithelium.由于脏层上皮局部脱离导致肾小球通透性改变。
Kidney Int. 1982 Apr;21(4):565-74. doi: 10.1038/ki.1982.63.
6
Proteinuria and structural alterations in rat glomerular basement membranes induced by intravenously injected anti-laminin immunoglobulin G.静脉注射抗层粘连蛋白免疫球蛋白G诱导大鼠肾小球基底膜的蛋白尿和结构改变
J Exp Med. 1982 Jul 1;156(1):128-45. doi: 10.1084/jem.156.1.128.
7
Laminin in glomerular basement membranes of aminonucleoside nephrotic rats. Increased proteinuria induced by antilaminin immunoglobulin G.氨基核苷肾病大鼠肾小球基底膜中的层粘连蛋白。抗层粘连蛋白免疫球蛋白G诱导蛋白尿增加。
Lab Invest. 1983 Jul;49(1):38-47.
8
Involvement of modulation of cell coat glycosaminoglycans in guinea pig peritoneal macrophage activity.豚鼠腹腔巨噬细胞活性中细胞被糖胺聚糖调节的参与情况。
J Reticuloendothel Soc. 1980 Apr;27(4):383-91.
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Isolation of a heparan sulfate-containing proteoglycan from basement membrane.从基底膜中分离出一种含硫酸乙酰肝素的蛋白聚糖。
Proc Natl Acad Sci U S A. 1980 Aug;77(8):4494-8. doi: 10.1073/pnas.77.8.4494.
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Increased permeability of the glomerular basement membrane to ferritin after removal of glycosaminoglycans (heparan sulfate) by enzyme digestion.通过酶消化去除糖胺聚糖(硫酸乙酰肝素)后,肾小球基底膜对铁蛋白的通透性增加。
J Cell Biol. 1980 Aug;86(2):688-93. doi: 10.1083/jcb.86.2.688.