谷氨酰胺对大剂量顺铂用药后大鼠肠道微生态影响的实验研究

Effects of glutamine on intestinal microecology after a high-dose cisplatin adminstration in rats

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 observe the effects of glutamine （Gln） supplementation on morphosis and mieroecologieal changes of intestinal mucosa in rats after a high-dose cisplatin （DDP） injection. Methods 30 SD rats were divided randomly into DDP group, DDP ＋ Gin group and normal saline （NS） control group according to body weight. 10 mg/kg DDP was injected intraperitonally, and 1 g/（ kg · d） Gln was given by oral gavage 3 days before DDP injection, and the same volume of water were used as the control. 48 hours later, blood samples of rats were obtained and blood urea nitrogen （BUN） and ereatinine （CRE） were measured by automatic biochemistry analyzer. Ileocecal lymph nodes were taken, and bacteria were cultured after homogenation under sterile conditions. At the same time the contents in jejunum, ileum and colon were smeared directly on the slides for bacteriological examination, and a histopathological examination of the terminal ileum specimens was performed. Resuits The rats suffered with acute renal failure at 48 hours after DDP administration. A series of pathological changes including mucosal hydropsia, decreased villous height with partial damage and shallower crypt depths were seen in ileum of rats after DDP injection, and the proportions of gram-negative bacteria within each part of intestine were significantly higher than that of control rats （ P 〈 0.01 ）. The positive rate of gram-negative bacilli grown in ileocecal lymph nodes was 80% in rats with DDP treatment ; while there was no bacterial translocation in control rats. After Gin intervention, plasma BUN and CRE levels of rats were slightly lower in DDP ＋ Gin group than that in DDP group, but they were significantly higher than that in control rats （ P 〈 0. O1 ）. Intestine hydropsia was obviously attenuated and intestinal villus structure was nearly normal. Although the proportions of gram-negative bacteria within each part of intestine were still higher than that of both control rats and DDP treatment rats, the bacterial transloeation rate in rats of combination group significantly decreased to 30% （ P 〈 0.01 ）. Conclusion Glu supplementation could play an important role in protecting intestinal mueosal barrier and attenuating bacterial transloeation, but had no significant preventive effects on acute renal failure and intestinal flora imbalance induced by high-dose DDP in rats.