Nomura A, Morita Y, Maruyama S, Hotta N, Nadai M, Wang L, Hasegawa T, Matsuo S
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Am J Pathol. 1997 Aug;151(2):539-47.
The present work was designed to elucidate the in vivo role of complement in the proteinuria-associated tubulointerstitial injury. Rats were intravenously injected with puromycin aminonucleoside, and massive proteinuria was observed within 5 days. Prominent tubulointerstitial injury characterized by proximal tubular degeneration, tubular dilatation, and leukocyte infiltration were observed 7 days after injection. C3 and C5b-9 were observed in the luminal side of proximal tubular cells. Renal function, assessed by inulin and para-aminohippurate clearance, was significantly decreased. To-assess the role of complement in this model, rats were injected with either cobra venom factor or soluble recombinant human complement receptor type 1 starting at day 3. These manipulations significantly improved tubulointerstitial pathology and para-aminohippurate clearance without affecting the degree of proteinuria. Deposition of C3 and C5b-9 was not detected in the kidney of rats depleted of complement by cobra venom factor. In rats treated with soluble complement receptor, C3 was still detected in the tubules, but deposition of C5b-9 was not observed. Soluble complement receptor was detected at the site of C3 deposition and in the urine. These data strongly suggest that complement plays a pivotal role in proteinuria-associated tubulointerstitial injury and that systemic complement depletion or inhibition of complement in the tubular lumen may diminish the tubulointerstitial damage.
本研究旨在阐明补体在蛋白尿相关的肾小管间质损伤中的体内作用。给大鼠静脉注射嘌呤霉素氨基核苷，5天内观察到大量蛋白尿。注射7天后观察到以近端肾小管变性、肾小管扩张和白细胞浸润为特征的显著肾小管间质损伤。在近端肾小管细胞的管腔侧观察到C3和C5b-9。通过菊粉和对氨基马尿酸清除率评估的肾功能显著下降。为了评估补体在该模型中的作用，从第3天开始给大鼠注射眼镜蛇毒因子或可溶性重组人补体受体1型。这些操作显著改善了肾小管间质病理和对氨基马尿酸清除率，而不影响蛋白尿程度。在经眼镜蛇毒因子耗尽补体的大鼠肾脏中未检测到C3和C5b-9的沉积。在用可溶性补体受体治疗的大鼠中，肾小管中仍可检测到C3，但未观察到C5b-9的沉积。在C3沉积部位和尿液中检测到可溶性补体受体。这些数据强烈表明补体在蛋白尿相关的肾小管间质损伤中起关键作用，并且全身补体耗竭或肾小管腔中补体的抑制可能减轻肾小管间质损伤。
