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簇集蛋白缺失会加重离体灌注肾脏中的免疫性肾小球损伤。

Clusterin depletion enhances immune glomerular injury in the isolated perfused kidney.

作者信息

Saunders J R, Aminian A, McRae J L, O'Farrell K A, Adam W R, Murphy B F

机构信息

Department of Nephrology, St. Vincent's Hospital, Melbourne, Victoria, Australia.

出版信息

Kidney Int. 1994 Mar;45(3):817-27. doi: 10.1038/ki.1994.108.

DOI:10.1038/ki.1994.108
PMID:8196284
Abstract

Clusterin is a normal plasma protein, shown to be an inhibitor of reactive complement hemolysis and a component of the fluid phase SC5b-9 terminal complement complexes. It is a component of glomerular immune deposits in human and experimental glomerulonephritis. Using the complement-dependent isolated perfused rat kidney model of autologous phase passive Heymann nephritis, we have studied the effect of clusterin depletion of perfused plasma on the development of glomerular injury. Kidneys with planted glomerular sheep anti-rat Fx1A antibody were perfused with human plasma either depleted of clusterin to < or = 30%, or control plasma depleted of plasma fibronectin. Glomerular injury was then initiated by the addition of guinea pig anti-sheep immunoglobulins to the perfusate. Kidneys perfused with clusterin depleted plasma developed significantly greater proteinuria at all time points when compared to control kidneys. Glomerular antibody binding and C3 deposition were similar in the two groups, but terminal complement components were deposited in larger amounts in the clusterin depleted group. These data support a possible role for clusterin in vivo in the protection of complement-induced glomerular injury.

摘要

簇集素是一种正常的血浆蛋白,被证明是反应性补体溶血的抑制剂以及液相SC5b - 9末端补体复合物的一个组成部分。它是人类和实验性肾小球肾炎中肾小球免疫沉积物的一个组成部分。利用自体相被动海曼肾炎的补体依赖性离体灌注大鼠肾脏模型,我们研究了灌注血浆中簇集素缺失对肾小球损伤发展的影响。用已将簇集素缺失至≤30%的人血浆或已将血浆纤连蛋白缺失的对照血浆灌注植入了肾小球羊抗大鼠Fx1A抗体的肾脏。然后通过向灌注液中加入豚鼠抗羊免疫球蛋白引发肾小球损伤。与对照肾脏相比,用簇集素缺失血浆灌注的肾脏在所有时间点都出现了明显更多的蛋白尿。两组中的肾小球抗体结合和C3沉积相似,但簇集素缺失组中末端补体成分的沉积量更大。这些数据支持簇集素在体内对补体诱导的肾小球损伤可能具有保护作用。

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Clusterin depletion enhances immune glomerular injury in the isolated perfused kidney.簇集蛋白缺失会加重离体灌注肾脏中的免疫性肾小球损伤。
Kidney Int. 1994 Mar;45(3):817-27. doi: 10.1038/ki.1994.108.
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