内毒素在大剂量顺铂所致大鼠急性肾损伤过程中的变化及意义

目的利用大剂量顺铂（cisplatin，DDP）所致大鼠急性肾功能衰竭的动物模型，观察外周血内毒素（endotoxin）在大鼠急性肾损伤中的变化及其意义。方法SD大鼠36只，雌雄各半，依体重随机分为DDP用药6h、48h、对照组和生理盐水（NS）用药6h、48h、对照组，每组6只。10mg／kgDDP单次腹腔内注射，等量Ns对照。观察并记录用药后对照组大鼠的毒副反应；用药6、48h各组大鼠无菌条件下心脏穿刺取血、肝素抗凝，检测外周血内毒素含量，同时内眦静脉取血，测定血清尿素氮、肌酐浓度，并进行统计学分析。结果DDP用药后6h，大鼠体重开始明显降低，用药48h后，大鼠腹泻逐渐加重，用药3d后大鼠死亡。DDP用药后6h大鼠血尿素氮、肌酐的含量与对照组比较差异无显著性（P〉0．05）；DDP用药后48h血尿素氮升至（18．71±9．9）mmol／L，明显高于对照组（7．48±0．6）mmol／L（P〈0．05），同时血肌酐含量亦升至（49．6±14．1）μmol／L，与对照组（27．17±1．7）μmol／L比较差异具有显著性（P〈0．05）。DDP用药后6h所有大鼠外周血内毒素含量都低于0．0218Eu／rrd最低检出限，明显低于NS对照组大鼠（0．3141±0．1477）Eu／ml（P〈0．01）；DDP用药后48h大鼠外周血内毒素的含量增高均超过0．70Eu／ml最高检出限，明显高于NS对照组大鼠（0．1661±0．1198）Eu／ml（P〈0．01）。结论外周血内毒素含量的变化与大剂量顺铂所致大鼠急性肾损伤早期的发病机制无关，但与大鼠肾功能衰竭有关的发生相关。

Significance of blood endotoxin in acute renal failure induced by high-dose cisplatin in rats

Objective To study the relationship between plasma endotoxin and renal function in acute renal failure induced by hlgh-dose cisplatin （DDP） in rats. Method 36 SD rats were divided randomly into 6 groups ： DDP 6 h, DDP 48 h,DDP control,normal saline （NS） 6 h,48 h and NS control group （n =6 in each group）. 10 mg/kg DDP was injected intraperitoneal/y while same volume of natural saline was given as the control. Toxic effects of DDP were observed subsequently. Heparinized blood samples were obtained by heart punctures 6 h and 48 h after DDP and NS administration and plasma endotoxin was measured by using the BET-16 bacterium endotoxin eryoscope. At the same time blood samples were obtained from orbital venous sinus and blood urea nitrogen （BUN） and creatinine （Cre） were measured by automatic biochemistry analyzer. Result Body weight of the rats decreased significantly at 6 h after DDP administration; diarrhea increased progressively at 48 h after DDP administration and the rats died in 3 d. There were no significant differences in blood BUN and creafinine between cisplatin group and control group 6 hours after administrations （ P 〉 0.05 ） ; Blood BUN and Cre increased to （ 18.71 ±9.9） mmol/L and （49.6 ± 14.1 ） μmol]/L respectively in rats 48 h after DDP administrations, significantly higher than the （7.48 ±0.6） mmol/L and （27.17 ± 1.7） μmol/L in control group （P 〈0.05）. Plasma endotoxin decreased below the detection limit of 0.0218 Eu/ml 6 h after DDP administration, significantly lower than the （0.3141 ± 0. 1477） Eu/ml in control group （ P 〈 0. 01 ）, while it increased above the detection limit of 0.70 Eu/ml 48 h after DDP administration, obviously higher than the （0. 1661 ± 0.1198）Eu/ml in control group （P 〈 0.01 ）. Conclusion Although there was no positive correlation between plasma endotoxin and renal injure in 6 h after DDP administration, the increase of plasma endotoxin may be an important pathophysiological factor of eisplatin-indu