大剂量顺铂所致大鼠急性肾功能衰竭过程中内毒素血症与革兰阴性菌感染的关系

Relationship between endotoxemia and gram negative bacillus infection in acute renal failure induced by high-dose cisplatin in rats

[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,探讨大鼠内毒素血症与革兰阴性菌感染的相互关系。[方法]SD大鼠24只,雌雄各半,依体重随机分为DDP用药6、24、48 h组和NS对照组,每组6只。10 mg/kg DDP单次腹腔内注射,等量生理盐水对照。观察并记录DDP用药后大鼠的反应及体重变化;心室穿刺取血行细菌培养和内毒素检测,内眦静脉取血检测肾脏功能,剖腹取回盲部淋巴结细菌培养。[结果]大剂量DDP用药后6 h大鼠体重开始进行性下降,用药48 h后大鼠出现腹泻,用药3 d后腹泻大鼠全部死亡。DDP用药后6 h所有大鼠外周血内毒素含量都低于0.0218 Eu/mL最低检出限,明显低于对照组大鼠(0.3141±0.2945)Eu/mL;DDP用药48 h后大鼠外周血内毒素含量显著增高,超出最高检出限0.70 Eu/mL,与对照组比较差异有显著性意义(P<0.01)。DDP用药后6、24、48 h大鼠和对照组大鼠,其外周血细菌培养均无细菌生长。DDP用药后24 h,66%的大鼠回盲部淋巴结发现革兰阴性菌生长;DDP用药后48 h,83%的大鼠回盲部淋巴结有革兰阴性菌生长,而对照组大鼠则无细菌生长。[结论]大剂量顺铂所致大鼠急性肾功能衰竭过程中,大鼠内毒素血症与其回盲部淋巴结革兰阴性菌感染有关,而与革兰阴性菌败血症无关。

[ Objective] To study the relationship between endotoxemia and gram negative bacillus infection in acute renal failure induced by high-dose cisplatin （DDP） in rats. [ Methods] SD rats 24 were divided randomly into 4 groups： DDP administration 6,24,48 h and normal saline （NS） control group （ n = 6 in each group）. 10 mg/kg DDP was injected intrap-eritoneally and the same volume of NS was given as control. Toxic effects of DDP were observed subsequently. Blood samples of rats treated with DDP or NS were obtained through heart punctures at 6,24 and 48 h after DDP administration. Plasma endotoxin was measured by using the BET - 16 bacterium endotoxin cryoscope and bacteria were cultured in blood. Blood urea nitrogen （BUN） and creatinine （Cre） were measured by the automatic biochemistry analyzer. At the same time ileocecal lymph nodes were taken, and bacteria were cultured after homogenated under sterile conditions. [ Results] Body weight of the rats started to decrease significantly at 6 h after DDP administration; Diarrhea appeared at 48 h after DDP administration. All the rats suffered from diarrhea died in 3 d. Plasma endotoxin in all rats decreased to the level lower than 0. 0218 Eu/mL （the lowest detection limit） at 6 h after DDP administration, significantly lower than that （0.3141±0. 2945 ）Eu/ mL in control group （P 〈 0.01 ）. But plasma endotoxin increased remarkably to the level higher than 0.70 Eu/mL（ the highest detection limit） at 48 h after DDP administration,obviously higher than that in control rats （P 〈 0.01 ）. No bacteria were found in the blood of all rats treated with or without DDP. Gram negative bacillus were found in the samples of ileocecal lymph node 66% of rats at 24 h after DDP administration,83% of rats at 48 h after DDP administration,but there was no bacteria growing in the samples of ileocecal lymph node in control rats. [ Conclusion ] Endotoxemia during acute renal failure induced by high - dose DDP in rats was related with gram negative bacillus infection in ileocecal lymph nodes but not gram negative bacteria sepsis.