粪菌移植对脓毒症小鼠血清炎性因子和肠损伤的影响

Effects of Fecal Microbiota Transplantation on Serum Inflammatory Factors and Intestinal Injury in Sepsis Mice

摘要: 目的：探讨粪菌移植技术对脓毒症小鼠肠粘膜屏障的影响。方法：按随机数字表法将75只雄性ICR小鼠分为3组：假手术组、脓毒症组和脓毒症 + 粪菌移植组，每组25只。采用盲肠结扎穿孔方法制作脓毒症小鼠模型。各组取10只小鼠观察7 d存活率；剩余小鼠分别于制模后12、24、48 h心脏取血后各处死5只，测定血清IL-6、IL-10、TNF-α和高迁移率族蛋白B1(HMGB1)水平；并在光镜下观察脓毒症小鼠小肠组织病理学改变并进行评分。结果：粪菌移植治疗组小鼠7 d存活率较脓毒症组小鼠组改善(P < 0.05)；与假手术组比较，脓毒症组造模后12、24及48 h血清IL-6、IL-10、TNF-α、HMGB1均有差异(P < 0.05)；与脓毒症组相比，在造模后12、24及48 h粪菌治疗干预后，粪菌移植组小鼠的血清TNF-α、IL-6、IL-10及HMGB1均明显下降(P < 0.05)，但仍高于假手术组(P < 0.05)；光镜下小肠组织病理学改变，与假手术组相比，在造模后12、24及48 h，脓毒症组小鼠肠组织损伤评分明显升高(P < 0.05)；与脓毒症组相比，造模后12 h粪菌移植组小鼠肠组织损伤评分无显著差异(P > 0.05)，而24、48 h的时间点粪菌移植组小鼠肠组织损伤评分偏低(P < 0.05)。结论：粪菌移植治疗能够降低严重脓毒症小鼠炎症反应并减轻由其引起的肠组织损伤，从而改善脓毒症进程，提高存活率。

Abstract: Objective: To investigate the effects of fecal microbiota transplantation on serum inflammatory fac-tors and intestinal injury in mice with sepsis. Methods: A total of 75 male C57BL/6 mice were ran-domly and equally divided into three groups: sham operation, sepsis, and sepsis + fecal microbiota transplantation. Severe sepsis model was induced by cecal ligation and puncture in mice. Ten mice in each group were monitored for the 7-d survival rate, and the remaining were killed 12, 24, and 48 h after the model was established. The levels of IL-6, IL-10, and high mobility group protein B1 (HMGB1) were measured. Results: The 7-day survival rate of severe sepsis mice was 0, and the 7-day survival rate of fecal bacteria transplantation group was increased to 50%; the difference was statistically significant compared to the model group (P < 0.05). Compared to the sham operation group, the sepsis group had higher serum creatinine levels at 12, 24, and 48 h after modeling, and the levels of TNF-α, IL-6, IL-10, and HMGB1 were significantly increased (P < 0.05). Compared to the sepsis group, the levels of serum TNF-a, IL-6, IL-10, and HMGB1 in the fecal bacteria transplantation group were significantly decreased (P < 0.05) after 12, 24, and 48 h of fecal bacteria treatment (P < 0.05), but still higher than those in the sham operation group (P < 0.05). Compared to the sepsis group, the intestinal tissue injury score of the fecal bacteria transplantation group did not show a significant difference at 12 h after modeling (P > 0.05), but the intestinal tissue injury score of the fecal bacteria transplantation group was lower at 24 and 48 h after modeling (P < 0.05). Conclusion: Fecal microbiota transplantation decreases the inflammatory response and intestinal tissue dam-age in severe sepsis mice and improves the survival rate.