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单侧肾切除对大鼠氯化汞肾毒性的影响。

The effect of unilateral nephrectomy on the nephrotoxicity of mercuric chloride in the rat.

作者信息

Houser M T, Berndt W O

出版信息

Toxicol Appl Pharmacol. 1986 May;83(3):506-15. doi: 10.1016/0041-008x(86)90233-4.

Abstract

Unilateral nephrectomy (UNX) induces a dramatic change in single-kidney structure and function. Therefore, the effects of nephrotoxins may be altered. To evaluate this possibility, mercuric chloride (2 mg/kg, sc) was given to male, Sprague-Dawley rats 2 days following either UNX or sham surgery. Nonoliguric acute renal failure developed and was qualitatively similar in both groups. Glomerular filtration rate (GFR) reached a nadir on Day 2 and was reduced to a greater extent in the UNX group. Furthermore, recovery of GFR was slower and occurred to a lesser extent by Day 10 in the animals subjected to UNX. Evidence of significant tubular dysfunction was present during the acute phase in both groups, as reflected by changes in the fractional excretion of sodium or lysozyme. Persistent tubular dysfunction was noted on Day 10 in both the sham and UNX groups, but the degree of dysfunction was greater in the UNX animals. The in vitro uptake of organic ions by renal cortical slices was reduced 24 hr following the injection of mercuric chloride although no difference was seen between the experimental groups. Mercury content within renal cortex was not increased in the UNX group at 1 or 3 hr but was higher 24 hr postinjection. Total urinary mercury excretion during the first day was not altered by UNX although single-kidney excretion was increased dramatically. These studies suggest that rats are more susceptible to mercuric chloride-induced nephrotoxicity 2 days following UNX. Although the mechanism(s) of this enhanced injury remains unclear, it does not appear to be completely related to an increase in renal cortical mercury content.

摘要

单侧肾切除(UNX)会引起单肾结构和功能的显著变化。因此,肾毒素的作用可能会改变。为评估这种可能性,在UNX或假手术后2天,给雄性Sprague-Dawley大鼠皮下注射氯化汞(2mg/kg)。两组均发生了非少尿型急性肾衰竭,且在性质上相似。肾小球滤过率(GFR)在第2天降至最低点,且在UNX组中降低幅度更大。此外,在接受UNX的动物中,GFR的恢复较慢,到第10天时恢复程度较小。两组在急性期均存在明显的肾小管功能障碍证据,这可通过钠或溶菌酶的排泄分数变化反映出来。在第10天时,假手术组和UNX组均观察到持续性肾小管功能障碍,但UNX动物的功能障碍程度更大。注射氯化汞24小时后,肾皮质切片对有机离子的体外摄取减少,尽管实验组之间未观察到差异。在注射后1小时或3小时,UNX组肾皮质中的汞含量并未增加,但在注射后24小时时更高。UNX并未改变第一天的总尿汞排泄量,尽管单肾排泄量显著增加。这些研究表明,大鼠在UNX后2天对氯化汞诱导的肾毒性更敏感。尽管这种增强损伤的机制尚不清楚,但似乎并不完全与肾皮质汞含量的增加有关。

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