大剂量顺铂所致大鼠急性肾衰过程中肠道细菌易位与肠内菌群比例变化的关系

Study on the changes of intestinal flora during acute renal failure induced by high-dose cisplatin in rat

目的研究大剂量顺铂(cisplatin,DDP)所致大鼠急性肾功能衰竭过程中肠道细菌易位与肠内菌群比例变化的关系。方法SD大鼠24只,雌雄各半,依体重随机分为DDP用药后24、48、72 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。随后观察并记录大鼠用药后的表现及体重变化情况;DDP用药后不同时间点分别取用药组大鼠和对照组大鼠,称重后内眦静脉取血,生化法检测血清尿素氮和肌酐的浓度;无菌条件下剖腹取回盲部淋巴结进行细菌培养;同时取十二指肠、空肠、回肠和结肠段内容物进行细菌涂片检查。结果大剂量DDP用药后6 h大鼠体重开始降低,用药48 h后出现腹泻症状并进行性加重。DDP用药后48 h大鼠出现血尿素氮、肌酐的比例显著升高,与对照组比较差异有非常显著性(P<0.01)。DDP用药后24 h66%的大鼠回盲部淋巴结出现革兰阴性菌生长,用药后48 h革兰阴性菌生长的阳性率为83%,而对照组大鼠则无细菌生长。对照组大鼠十二指肠、空肠和回肠内主要以革兰阳性球菌为主,结肠内主要以革兰阴性杆菌和革兰阳性球菌为主。DDP用药后24 h,十二指肠、空肠、回肠和结肠内仍然以革兰阳性球菌为主;用药48 h后,空肠、回肠和结肠内革兰阴性杆菌所占比例逐渐增加。结论大剂量DDP可导致大鼠肠道细菌易位、空肠、回肠和结肠内菌群比例失衡,可能与大鼠内毒素血症及急性肾功能衰竭的发生、发展及恶化有关。

Objective To study the relationship between changes in the proportion of intestinal flora and ileocecal bacterial translocation in acute renal failure induced by high-dose cisplatin（DDP） in rats.Method 24 SD rats were divided randomly into 4 groups（n=6 in each group）.10 mg/kg DDP was injected intraperitoneally and the same volume of natural saline was given as control.Toxic effects of DDP were observed subsequently.Blood samples of rats were obtained from orbital venous sinus before and at 24 h,48 h,72 h after DDP administrations,and blood urea nitrogen（BUN） and creatinine（Cre） were measured by automatic biochemistry analyzer.Ileocecal lymph nodes were taken,and bacteria were cultured after homogenated under sterile conditions.At the same time the contents in duodenum,jejunum,ileum and colon were smeared directly on the slides for bacteriological examination.Result Body weights of rats decreased signifi-cantly in 6 h after DDP administration and diarrhea appeared and became aggravated in 48 h after DDP administration.Re-nal failure existed at 48 h after DDP administration.Gram-negative bacteria could be detected in Ileocecal lymph nodes of 66% rats 24 h after DDP administration,and in 83% rats 48 h after DDP administration,while no bacteria grew in control rats.Gram-positive cocci were seen mainly in duodenum,jejunum,ileum and colon,while Gram-negative bacilli and gram-positive cocci were dominant in colon.24 h after DDP administration,Gram-positive cocci were seen mainly in duodenum,jejunum,ileum and colon also.But in 48 h after DDP administration,the ratio of Gram-negative bacilli were gradually increased in jejunum,ileum and colon.Conclusion High-dose DDP can lead to not only bacterial translocation but also imbalance of intestinal flora in rats,which may be related to endotoxemia in rats and the incidence of acute renal failure,development and degradation.