Ishmael J, Pratt I, Lock E A
J Pathol. 1982 Oct;138(2):99-113. doi: 10.1002/path.1711380202.
Administration of hexachloro 1:3 butadiene (HCBD) intraperitoneally at a dose of 200 mg/kg body weight caused necrosis of the parts recta of the proximal tubules situated in the outer stripe of the outer medulla of the rat kidney. The earliest morphological changes detectable by light microscopy were observed after eight hours, with several proximal tubules showing necrosis. By sixteen hours a distinct band of tubular necrosis was seen in the outer stripe of the outer medulla. One and two days after dosing proximal tubular necrosis was still evident whereas distal tubules were unaffected. By three days, vacuolation was observed in the pars convoluta of some proximal tubules. Active tubular regeneration was apparent by day five, which was accompanied by a marked increase in renal water and nonprotein sulphydryl content (NP-SH). By day fourteen substantial recovery had occurred. Ultrastructural changes were seen as early as one hour after HCBD (300 mg/kg, ip) although necrosis was not marked until 8 hr. Mitochondrial swelling was seen 1-4 hr after dosing in the S1 and S2 segments of the proximal tubule. By 8 hr the major pathological changes were largely confined to the S2 segment and consisted of loss of brush border, mitochondrial swelling and cellular necrosis. In conclusion HCBD produces a site-specific nephrotoxic effect on the proximal tubule in the rat. The pattern of injury was similar to that associated with some other nephrotoxic and ischaemic models of acute renal failure.
以200毫克/千克体重的剂量腹腔注射六氯-1,3-丁二烯(HCBD)会导致大鼠肾脏外髓质外层条纹中近端小管直部坏死。光学显微镜下最早可检测到的形态学变化在8小时后观察到,有几个近端小管出现坏死。到16小时时,在外髓质外层条纹中可见明显的肾小管坏死带。给药后1天和2天,近端肾小管坏死仍然明显,而远端小管未受影响。到3天时,在一些近端小管的曲部观察到空泡化。到第5天,活跃的肾小管再生明显,同时肾脏水含量和非蛋白巯基含量(NP-SH)显著增加。到第14天时,已出现实质性恢复。超微结构变化早在腹腔注射HCBD(300毫克/千克)后1小时就可见到,尽管直到8小时坏死才明显。给药后1 - 4小时,在近端小管的S1和S2段可见线粒体肿胀。到8小时时,主要病理变化主要局限于S2段,包括刷状缘丧失、线粒体肿胀和细胞坏死。总之,HCBD对大鼠近端小管产生部位特异性肾毒性作用。损伤模式与其他一些肾毒性和急性肾衰竭缺血模型相关的模式相似。