SCID小鼠肠道菌群失调对深部白色念珠菌感染的影响研究

目的建立重度联合免疫缺陷（SCID）小鼠白色念珠菌感染模型，探讨肠道菌群失调与深部白色念珠菌感染的联系。方法SCID小鼠随机口服万古霉素水溶液7d，饥饿24h后给予白色念珠菌灌胃，建立小鼠白色念珠菌感染模型，观察小鼠死亡情况。荧光定量PCR检测肠道细菌总量、基质辅助激光解析电离飞行时间质谱仪鉴定肠道菌群种类，并应用扫描电镜观察肠壁黏膜组织超微结构的改变。结果应用万古霉素可致肠道菌群失调，肠道黏膜完整性受损。在万古霉素致肠道菌群失调的基础上，外源性白色念珠菌攻击可加重肠道菌群失调和肠壁黏膜损伤程度，促进深部白色念珠菌感染的发生。结论肠道菌群失衡可以导致深部白色念珠菌感染的发生，肠壁黏膜的完整性可能参与了肠道白色念珠菌播散过程。

The impact of intestinal microbiota imbalances on susceptibility to invasive Candida albicans infection in SCID mice

Objective To establish a severe combined immunodeficiency(SCID) mice model for invasive Candida albicans infection and study the relationship between imbalances of the intestinal microbiota and susceptibility to invasive Candida albicans infection.Method SCID mice were treated with 0.125 g/250 mL of vancomycin in drinking water for 7 days and were deprived of food for 24 hours.Then the mice were inoculated with 0.1 mL 1.5×109 or 1.5×105 CFU of Candida albicans by intragastric gavage.After the invasive Candida albicans infection model of SCID mice was established,death of the SCID mice were closely observed.Total number of intestinal bacteria were measured by real-time PCR using 16S rRNA gene primers;alterations of diversity of the intestinal microbiota were rapidly identified with matrix-assisted laser desorption ionization time-of-flight mass spectrometry;the pathological changes of intestinal mucosa were observed by scanning transmission electron microscope(SEM).Result Vancomycin caused the imbalance of intestinal microbiota and damage to intestinal mucosa.The Candida albicans attack had increased the damage of intestinal mucosa and promoted the occurrence of Candida albicans translocations after intestinal microbiota imbalance was induced.Conclusion The disruption of the intestinal microbiota alters the host susceptibility to Candida albicans infection and the integrity of intestinal mucosa may be also involved in the process of Candida albicans invasive infection.