急性镉染毒对大鼠肾脏线粒体的损伤

Rat kidney mitochondrial damage induced by acute cadmium administration

目的研究急性镉染毒对大鼠。肾脏线粒体形态和功能的影响。方法健康成年雄性SD大鼠随机分为4组，每组6只。分别给予大鼠皮下注射染镉0．6、1．2、1．8mg／kg（CdCl2），对照组注射相应容积生理盐水，每天1次，连续注射5d。用透射电子显微镜观察。肾脏线粒体超微结构变化，差速离心法制备大鼠肾脏线粒体，Clark氧电极法测定线粒体呼吸功能，荧光法测定线粒体膜电位，分光光度法测定线粒体肿胀，四唑盐（NBT）法测定线粒体超氧化物含量。结果电子显微镜观察显示，镉染毒对大鼠肾脏线粒体的损伤明显，表现为线粒体基质空泡增多、线粒体肿胀色泽加深。随染毒剂量的增加，大鼠肾脏线粒体损伤加重。与对照组相比，高剂量组线粒体Ⅲ态呼吸速率（V3）[（6．25±0．61）nmol／LO2·min-1·mg-1明显低于对照组[（9．66±1．16）nmol／LO2·min-·mg-1]，RCR值（2．45±0．23）亦明显降低，差异均有统计学意义（P〈0．01，P〈0．05），提示线粒体呼吸功能受阻；线粒体膜电位水平（85．89％±3．82％）明显低于对照组（100．00％±3．43％），差异有统计学意义（P〈0．05），而氧自由基水平（116．33％±3．06％）则较对照组（100．00％±2．25％）明显上升，差异亦有统计学意义（P〈0．05）。结论急性镉染毒可造成大鼠。肾脏线粒体损伤，引起线粒体呼吸功能受阻，膜电位降低，肿胀程度加剧，而这些损伤效应可能与线粒体内氧自由基水平增加有关。

Objective To evaluate effect of acute cadmium administration on mitochondria from rat kidney. Methods 24 male Spragne-Dawley （SD） rats were randomly divided into four groups. Four groups of rats were injected with saline, 0.6, 1.2, and 1.8 mg/kg weight subcutaneously,once daily, for 5 days, respec- tively. Ultrastructural change of rat kidney mitochondria was observed, and respiration function, membrane potential, mitochondria swelling, and superoxide level were determined. Results Ultrastruetural changes in- eluded matrix vaeuolation, swelling and condensation of mitoehondria. In group of 1.8 mg/kg body weight, the oxygen consumption rate during state 3 respiration [（6.25 ±0.61 ） nmol/L O2 ·min-· mg-1] and RCR value （2.45±0.23 ） were significantly lower than those of control group [ （9.66 ±1.16） nmol/L O2·min-1· mg-1] （p〈 0.05 ）, indicating respiration inhibition. The membrane pot ential and superoxide level of the same group were 85.89%±3.82% and 116.33%±3.06% of control values （P〈0.05）, respectively. Conclusions Acute cadmium administration can cause rat kidney mitochondrial damage in a dose-effect manner, including inhibition of respiration, dissipation of membrane potential, swelling of mitochondria matrix. Such damage might be related to the increase of mitochondrial free radical.