广谱抗生素对脓毒症大鼠肠道微生态环境的影响

Influence of broad-spectrum antibiotics on the gut microflora in sepsis in rats MA

目的探讨广谱抗生素对脓毒症大鼠肠道微生态环境的影响。方法56只健康SD大鼠被随机分为正常对照组、烫伤组和脓毒症组。于大鼠背部造成30％总体表面积Ⅲ度烫伤后24h，间隔12h分两次腹腔注射内毒素（20mg／kg）进行“二次打击”制备脓毒症模型。分别于烫伤及“二次打击”后24h，间隔12h分两次腹腔注射头孢曲松进行治疗，各组于治疗前及治疗3d和9d活杀8只大鼠，取胃窦、小肠、结肠内容物及结肠黏膜行细菌定量培养、菌种鉴定。结果单纯烫伤对结肠内容物杆菌数量和种类无明显影响，“二次打击”后，杆菌数升高上千倍（P〈0．01），应用头孢曲松治疗后大鼠结肠内容物杆菌数量明显减少（P均〈0．01），小肠内容物肠杆菌亦有类似变化，而胃内容物肠杆菌数量变化不显著。经烫伤及“二次打击”后肠道杆菌数量显著增加，球／杆比值负值增大；应用头孢曲松后，肠球菌数量显著增多，球／杆比值严重倒置；厌氧菌数量亦有所减少，但差异不显著。结论广谱抗生素使定植于肠道的厌氧菌和肠杆菌数量锐减，使肠球菌、耐药菌选择为优势菌群成为可能，造成肠道微生态环境破坏。

Objective To study the influence of broad-spectrum antibiotics on intestinal microecology in septic rats. Methods Fifty-six Sprague-Dawley （SD） rats were randomly divided into normal control, burn and sepsis group. Rats in the latter two groups received 30% total body surface area （TBSA） Ⅲ degree burns on back followed by an injection of endotoxin in a dose of 20 mg/kg 24 hours later. The animals in sepsis group were treated with intraperitoneal injection of ceftriaxone 12 hours after the endotoxin challenge in a dose of 60 mg/kg, and it was repeated 12 hours later. Another group of rats received burn injury only. Eight rats in burn group and sepsis group were sacrificed before ceftriaxone treatment, 3 days and 9 days after the treatment, respectively. The gastric, intestinal and colonic contents were collected for bacterial cultures and species determination. Results The influence of burn injury on the number and species of gut bacteria was not obvious. The addition of endotoxin could markedly increase the number of enteric bacilli in small intestine and colon （both P〈0.01）, but not in stomach. However, the number of enteric bacilli was sharply decreased in intestine and colon after ceftriaxone treatment （all P〈0.01）. Furthermore, the ratio of cocci to bacilli was seriously inverted in intestine and colon after ceftriaxone treatment, though burn injury followed by endotoxin had dramatically raise the ratio of cocci to bacilli in intestine and colon. It also produce a loss of anaerobic bacteria in colon, though the difference in number was not statistically significant. Conclusion Broad-spectrum antibiotics could decrease the amount of entericbacilli, making enterococci to be the predominant microbial flora in gut.