New features of renal lesion induced by stroma free hemoglobin
New features of renal lesion induced by stroma free hemoglobin
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DOI：
10.1177/019262330002800501
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发表时间：
2000-09-01
影响因子：
1.5
通讯作者：
Tam, MSC
中科院分区：
文献类型：
--
作者：
Chan, WL;Tang, NLS;Tam, MSC
这项研究的重点是输注基质游离血红蛋白 (SFH) 引起的亚急性肾脏损伤，尽管在急性输注中观察到有限的肾毒性，但仍将其作为潜在的血液替代品进行评估。四组大鼠接受不同剂量的 SFH（分别为 0.03、0.48、0.96 和 1.46 g），并在 10 天的过程中每隔几天监测其肾小球滤过率。另一组 6 只大鼠在第 10 天处死接受 0.96 g SFH 以检查肾脏形态。低剂量 (0.03 g) SFH 输注在 10 天内没有改变肌酐清除率 (Clcr)。接受 0.48 g SFH 的大鼠的 Clcr 下降，但在第 10 天完全恢复。在接受 0.96 和 1.68 g SFH 的大鼠组中观察到 Clcr 持续下降。肾小管坏死是最突出的肾脏病变，分布于近端肾小管，尤其是近髓肾单位的曲段。在幸存的近端小管中发现了珍珠染色的细胞质颗粒和电子致密的溶酶体颗粒。坏死是细胞死亡的主要机制。这项研究首次揭示了 SFH 治疗后近端肾小管中光滑内质网的增殖，其表现为肾小管泡状结构的结节状聚集体。 SFH 对近曲小管的作用似乎是直接毒性，并且这种毒性被证明是剂量依赖性的。可逆毒性的存在表明SFH输注存在安全限度剂量，临床应用可以确定SFH的耐受剂量。
This study focused on the subacute renal lesions resulting from the infusion of stroma free hemoglobin (SFH), which remains under evaluation as a potential blood substitute despite limited renal toxicity observed in acute infusion. Four groups of rats received different doses of SFH (0.03, 0.48, 0.96, and 1.46 g, respectively) and were monitored, on alternate days, for their glomerular filtration rate over the course of 10 days. Another group of 6 rats receiving 0.96 g SFH was sacrificed at day 10 for examination of renal morphology. The low dose (0.03 g) of SFH infusion did not alter the creatinine clearance (Clcr) over 10 days. The Clcr decreased in rats receiving 0.48 g SFH but fully recovered at day 10. A persistent decrease in Clcr was observed in the groups of rats receiving 0.96 and 1.68 g of SFH. Tubular necrosis was the most prominent renal lesion distributed in the proximal tubules, especially in the convoluted segment of the juxtamedullary nephrons. Pearls' stained cytoplasmic granules and electron-dense lysosomal granules were found in surviving proximal tubules. Necrosis was the predominant mechanism of cell death. This study revealed for the first time proliferation of smooth endoplasmic reticulum in the proximal tubules after SFH treatment, where it appeared as nodular aggregates of tubulovesicular structures. The effect of SFH on the proximal tubule appeared to be a direct toxicity, and this toxicity was shown to be dose dependent. The presence of reversible toxicity indicated that a safety limit dosage for SFH infusion exists and that tolerance dose of SFH can be determined for clinical applications.