Glomerular macrophage modulation affects mesangial expansion in the rat after renal ablation.

Glomerular macrophage modulation affects mesangial expansion in the rat after renal ablation.
复制标题

肾小球巨噬细胞的调节影响肾脏消融后大鼠的系膜扩张。

DOI:
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发表时间:
1992
期刊:
Laboratory investigation; a journal of technical methods and pathology
影响因子:
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通讯作者:
J. Grond
J. Grond
中科院分区:
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文献类型:
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作者:
H. Vangoor;van der Horst Ml;Fidler;J. Grond

文献摘要

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最近的研究提供了巨噬细胞(m phi)参与各种类型的人类和实验性肾小球疾病的证据。本研究的目的是检查m phi耗竭对大鼠3/4肾消融后肾小球损伤的影响。这种“残肾”模型是广泛使用的局灶性和节段性肾小球硬化的实验模型。通过亚致死剂量的三重全身X射线照射并屏蔽残肾,在残肾大鼠中诱导持续的肾小球M φ耗竭。在肾消融术后5、9和13周,对8只X射线照射和8只非照射大鼠进行了研究。X射线照射的大鼠表现出严重的外周血白细胞减少症,在5和9周,在13周正常化。与未照射的残肾大鼠相比,X射线照射大鼠5周时的残余肾小球m phi(单克隆抗体ED 1免疫组化)数量显著降低。放射线照射后9周和13周大鼠残余肾小球中m phi增加,出现反跳效应。光学显微镜检查显示,与未照射的残肾大鼠相比,在5周时X射线照射大鼠的残肾肾小球中,系膜细胞和系膜基质扩张的半定量评分显著降低。在X射线照射的大鼠中,在消融术后9周和13周肾小球系膜基质扩张增加,与这些时间间隔的肾小球m phi升高一致。多元线性回归分析表明,最佳拟合回归模型预测系膜基质扩张(多个r2 = 0.81)的高度显着的贡献m φ。总之,这些数据提供的证据表明,m phi在大鼠肾消融术后肾小球损伤的演变中起着重要作用。
Recent studies have provided evidence for the involvement of macrophages (m phi) in various types of human and experimental glomerular disease. The aim of the present study was to examine the effect of m phi depletion on glomerular injury after 3/4 renal ablation in the rat. This "remnant kidney" model is a widely used experimental model of focal and segmental glomerulosclerosis. Sustained glomerular m phi depletion was induced in remnant kidney rats by a regimen of sublethal triple systemic X-irradiation with shielding of the kidney remnants. Groups of 8 X-irradiated and 8 non-irradiated rats were studied at 5, 9, and 13 weeks after renal ablation. X-irradiated rats showed severe peripheral blood leukopenia at 5 and 9 weeks which had normalized at 13 weeks. The number of remnant glomerular m phi (immunohistochemistry with the monoclonal antibody ED1) in X-irradiated rats at 5 weeks was significantly lower when compared to non-irradiated remnant kidney rats. A rebound effect occurred at 9 and 13 weeks with increased m phi in remnant glomeruli of X-irradiated rats. Light microscopic examination disclosed significantly lower semiquantitative scores for mesangial cellularity and mesangial matrix expansion in remnant glomeruli of X-irradiated rats at 5 weeks when compared to non-irradiated remnant kidney rats. Mesangial matrix expansion had increased in X-irradiated rats at 9 and 13 weeks after ablation coincident with elevated glomerular m phi at these intervals. Multiple linear regression analysis indicated a highly significant contribution of m phi to the best fitting regression model predicting mesangial matrix expansion (multiple r2 = 0.81). In conclusion, these data provide evidence for a contributory role of m phi in the evolution of glomerular injury in the rat after renal ablation.