Dobyan D C, Bulger R E
Lab Invest. 1984 May;50(5):578-86.
Previous studies have demonstrated that the anesthetic amine, chlorpromazine hydrochloride (CPZ), prevents cell necrosis in experimentally induced ischemic liver and heart disease and decreases the extent of galactosamine-induced cell death in the liver. The present model was designed to determine whether CPZ exerts a similar beneficial effect in kidney in a nephrotoxic model of acute renal failure in rats induced by the administration of mercuric chloride (2 mg/kg of body weight). The functional and structural changes in the kidney were evaluated and quantitated in animals pretreated with CPZ (40 mg/kg of body weight) or saline and then subjected to nephrotoxic injury. Compared to controls, the glomerular filtration rate was significantly lower (p less than 0.001) in saline- and CPZ-pretreated rats receiving mercuric chloride. Twenty-four hours after mercuric chloride administration the glomerular filtration rate was 446 +/- 38 microl/minute/gm of kidney weight, the fractional sodium excretion was 0.4 +/- 0.2%, and the urinary osmolality was 1440 +/- 193 mOsmoles/kg of H2O in the CPZ-treated animals compared to 26 +/- 18 microl/minute/gm of kidney weight (p less than 0.001), 10.1 +/- 9.8% (p less than 0.025), and 353 +/- 28 mOsmoles/kg of H2O (p less than 0.005), respectively, in the animals receiving mercuric chloride alone. The percentage of proximal tubule cell necrosis was 26.5 +/- 8.9% in the CPZ-pretreated group compared to 88.1 +/- 3.6% in the untreated group (p less than 0.001). Metabolic cage studies were performed to follow the time course of this model for 48, 72, and 96 hours after mercury injection. The serum creatinine values and fractional sodium excretions were significantly less in animals receiving CPZ compared to the untreated group at all time intervals examined. The serum urea nitrogen concentration and glomerular filtration rate were similar for the two groups after 48 hours, but the serum urea nitrogen level was significantly lower and the glomerular filtration rate higher after 72 and 96 hours in the animals pretreated with CPZ. In agreement with these findings were observations that animals pretreated with CPZ had significantly fewer necrotic cells 48 and 72 hours after mercury administration, and tubular regeneration appeared to be markedly accelerated. These results suggest that pretreatment with CPZ markedly lessens the degree of structural and functional impairment seen in mercuric chloride-induced acute renal failure in rats and increases the rate of recovery.
先前的研究表明，麻醉性胺盐酸氯丙嗪（CPZ）可预防实验性诱导的缺血性肝病和心脏病中的细胞坏死，并减少半乳糖胺诱导的肝脏细胞死亡程度。本模型旨在确定CPZ在由氯化汞（2mg/kg体重）诱导的大鼠急性肾衰竭肾毒性模型中是否对肾脏产生类似的有益作用。对用CPZ（40mg/kg体重）或生理盐水预处理后再遭受肾毒性损伤的动物的肾脏功能和结构变化进行评估和定量。与对照组相比，接受氯化汞的生理盐水预处理组和CPZ预处理组大鼠的肾小球滤过率显著更低（p<0.001）。在给予氯化汞24小时后，CPZ处理组动物的肾小球滤过率为446±38微升/分钟/克肾重，钠排泄分数为0.4±0.2%，尿渗透压为1440±193毫摩尔/千克水，而单独接受氯化汞的动物分别为26±18微升/分钟/克肾重（p<0.001）、10.1±9.8%（p<0.025）和353±28毫摩尔/千克水（p<0.005）。CPZ预处理组近端肾小管细胞坏死百分比为26.5±8.9%，而未处理组为88.1±3.6%（p<0.001）。进行代谢笼研究以追踪该模型在注射汞后48、72和96小时的时间进程。在所有检查的时间间隔内，接受CPZ的动物的血清肌酐值和钠排泄分数均显著低于未处理组。48小时后两组的血清尿素氮浓度和肾小球滤过率相似，但在72和96小时后，CPZ预处理的动物血清尿素氮水平显著更低，肾小球滤过率更高。与这些发现一致的是，观察到CPZ预处理的动物在给予汞后48和72小时坏死细胞明显更少，并且肾小管再生似乎明显加速。这些结果表明，CPZ预处理可显著减轻氯化汞诱导的大鼠急性肾衰竭中所见的结构和功能损害程度，并提高恢复率。
