目的探讨谷氨酰胺(glutamine,Gln)对大剂量顺铂(cisplatin,DDP)用药后大鼠肠道菌群失衡及细菌易位和肠黏膜形态的影响。方法 SD大鼠30只,雌雄各半,依体重随机分为3组:DDP用药组、DDP与Gln联合用药组及生理盐水(NS)对照组,每组10只。10 mg/kg DDP单次腹腔内注射,等量NS腹腔内注射对照;DDP用药前3 d开始,联合用药组大鼠Gln 1 g/(kg.d)灌胃,等量水灌胃对照。DDP用药后48 h,各组大鼠麻醉后内眦静脉取血测血清尿素氮(BUN)、肌酐(CRE)含量;无菌条件下剖腹取回盲部淋巴结匀浆后细菌培养;取空肠、回肠和结肠段内容物细菌涂片检查肠内菌群比例的变化;取回肠黏膜组织检查形态学改变。结果 DDP用药后48 h,DDP用药组大鼠血BUN和CRE含量明显升高,出现急性肾功能衰竭;黏膜水肿明显、绒毛短缩部分破坏、隐窝变浅;各段肠管内革兰阴性杆菌所占比例较对照明显增高(P<0.01);回盲部淋巴结革兰阴性菌阳性率为80%,而对照组大鼠回盲部淋巴结无细菌生长。DDP用药后48 h,联合用药组大鼠血BUN和CRE含量略低于DDP用药组大鼠,但仍明显高于对照组大鼠(P<0.01);大鼠回肠黏膜水肿较DDP用药组大鼠明显减轻、绒毛破坏不明显;回肠内革兰阴性杆菌所占比例明显高于DDP用药组大鼠(P<0.01),各段肠管内革兰阴性杆菌所占比例亦明显高于对照组大鼠(P<0.01);回盲部淋巴结革兰阴性菌阳性率为30%,明显低于DDP用药组大鼠。结论大剂量DDP在引起大鼠急性肾功能衰竭的同时,亦可导致大鼠肠黏膜损伤、肠道内菌群失衡,并出现肠源性细菌易位。Gln具有保护肠黏膜、减少肠源性细菌易位的功能,但对大剂量DDP所致肠道内菌群失衡及急性肾功能衰竭无明显防治作用。 Objective To investigate the effects of glutamine (Gln) on the imbalance of intestinal flora, bacterial translocation and intestinal mucosal morphology after administration of high dose cisplatin (DDP) in rats. Methods Thirty male SD rats were randomly divided into 3 groups: DDP group, DDP and Gln combination group and saline (NS) control group, 10 rats in each group. A single intraperitoneal injection of 10 mg/kg DDP was administered intraperitoneally with equal doses of NS. DND was given 3 days before the administration of DDP. Rats in the combination group were given g 1 g/(kg.d) gavage and the same amount of water was given to the control. At 48 hours after DDP administration, blood was collected from the internal hemorrhoids to measure serum urea nitrogen (BUN) and creatinine (CRE) levels after anesthesia in all groups; under aseptic conditions, bacterial culture was performed by resection of blinded lymph nodes homogenate under sterile conditions; Bacterial smears of the contents of the ileum and colon were used to examine changes in the proportion of intestinal flora; morphological changes were taken from the ileal mucosa. Results At 48 h after DDP administration, the BUN and CRE contents in the DDP-treated group increased significantly and acute renal failure occurred. The mucosal edema was evident, the villous shortening was partially destroyed, and the crypts became lighter; gram-negative bacilli in the intestinal tract of each segment were observed. The proportion was significantly higher than that of the control (P<0.01); the positive rate of gram-negative bacteria in the ileocecal lymph nodes was 80%, while there was no bacterial growth in the ileocecal lymph nodes of the control group. At 48 h after administration of DDP, BUN and CRE levels in the combined treatment group were slightly lower than those in the DDP group, but were still significantly higher than those in the control group (P<0.01). Rat ileal mucosal edema was greater than that in the DDP group. Rats significantly reduced, and villous destruction was not obvious; the proportion of gram-negative bacilli in the ileum was significantly higher than that in the DDP-administered group (P<0.01), and the proportion of gram-negative bacilli in the intestinal tract was also significantly higher in the ileum than in the control group. Rats (P<0.01); The positive rate of gram-negative bacteria in ileocecal lymph nodes was 30%, which was significantly lower than that of DDP-administered rats. Conclusions High-dose DDP can cause acute renal failure in rats, as well as intestinal mucosal damage, intestinal flora imbalance, and intestinal bacterial translocation. Gln has the function of protecting the intestinal mucosa and reducing the translocation of intestinal bacteria, but it has no obvious preventive effect on the imbalance of intestinal flora caused by high-dose DDP and acute renal failure.