Renal Tubulointerstitial Lesions in Mercuric Chloride-Treated Brown Norway Rats

Renal Tubulointerstitial Lesions in Mercuric Chloride-Treated Brown Norway Rats
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氯化汞治疗棕色挪威大鼠的肾小管间质病变

DOI:
10.1293/tox.11.241
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发表时间:
1998
影响因子:
1.2
通讯作者:
K. Doi
K. Doi
中科院分区:
医学4区
文献类型:
--
作者:
Kazuhiko Suzuki;K. Uetsuka;H. Nakayama;C. Doi;K. Doi

文献摘要

被引文献

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研究了氯化汞处理的褐挪威大鼠肾小管间质病变,重点研究了病变的发生与浸润细胞动力学和α-平滑肌肌动蛋白(SMA)阳性肌成纤维细胞的关系。15只大鼠于第0天注射氯化汞1 mg/kg b.w.,第2、4、6天分别处死5只大鼠。另外20只大鼠在第0、2、4天注射相同剂量的氯化汞,在第6、8、10、20天分别杀死5只大鼠。肾小球未发现其他变化,而主要在近端小管中,第2天坏死明显,第4天再生变化明显,第6天及之后受累小管扩张伴小管周围纤维化。肾上皮损伤后第6天及之后,肾间质出现单核细胞浸润,浸润细胞中ed1阳性巨噬细胞居多,cd8阳性T细胞次之。在注射三次氯化汞后的第2天,即第6天,它们开始显著增加。此外,α- sma阳性的肌成纤维细胞数量在第6天和第6天后也有所增加,ed1阳性的巨噬细胞的动力学与α- sma阳性的肌成纤维细胞的动力学基本一致。肾间质纤维化随着这两种细胞群数量的增加而发展。其他浸润细胞虽然绝对数量很少,但cd45ra阳性B细胞在第10天及之后均显著增加。少量cd4阳性T细胞和ed2阳性T细胞也观察到,但它们的数量没有明显变化。目前的研究结果表明,ed1阳性巨噬细胞和α- sma阳性肌成纤维细胞参与氯化汞处理后褐挪威大鼠肾纤维化,尽管淋巴细胞在肾纤维化中的作用尚不清楚。
Renal tubulointerstitial lesions in mercuric chloride-treated Brown Norway rats were investigated focusing on the relationship between the development of lesions and kinetics of infiltrating cells and α-smooth muscle actin (SMA)-positive myofibroblasts. Fifteen rats were injected with 1 mg/kg b.w. of mercuric chloride at day 0, and 5 rats were killed at days 2, 4, and 6, respectively. Another 20 rats were injected with the same dose of mercuric chloride at days 0, 2 and 4, and 5 rats were killed at days 6, 8, 10, and 20, respectively. No additional changes were detected in glomeruli, whereas, mainly in the proximal tubules, necrosis was prominent at day 2, regenerative changes were obvious at day 4, and dilatation of the affected tubules with peritubular fibrosis developed at and after day 6. Following the renal epithelial damage, mononuclear cell infiltration developed in the renal interstitium at and after day 6, and among the infiltrating cells, ED1-positive macrophages were most predominant and CD8-positive T cells were next throughout the experimental period. They began to increases prominently at 2 days after 3 injections of mercuric chloride, i.e. at day 6. In addition, the number of α-SMA-positive myofibroblasts also increased at and after day 6, and the kinetics of ED1-positive macrophages corresponded well with that of α-SMA-positive myofibroblasts. Renal interstitial fibrosis developed along with the increase in numbers of these two cell populations. As to other infiltrating cells, although the absolute number was very small, CD45RA-positive B cells significantly increased at and after day 10. A few CD4-positive T cells and ED2-positive cells were also observed but their numbers did not show significant changes. The present results indicate that ED1-positive macrophages and α-SMA-positive myofibroblasts participate in renal fibrosis in Brown Norway rats following mercuric chloride-treatment, although the role of lymphocytes in renal fibrosis is still obscure.