口服鼠李糖乳杆菌GG减轻鼠衣原体感染引起的上生殖道病变  

Lactobacillus rhamnosus GG attenuates the pathology of Chlamydial muridarium in the upper genital tract in mice

作　　者：周曾梓 孙信[1] 张琪[1] 曾飞[1] 尹嘉欣 王陆颖[1] ZHOU Zengzi;SUN Xin;ZHANG Qi;ZENG Fei;YIN Jiaxin;WANG Luying(Department of Obstetrics and Gynecology,Third Xiangya Hospital,Central South University,Changsha 410013;Department of Obstetrics and Gynecology,Jingzhou People's Hospital,Huaihua Hunan 418400,China)

机构地区：[1]中南大学湘雅三医院妇产科,长沙410013 [2]湖南省靖州人民医院妇产科,湖南怀化418400

出　　处：《中南大学学报（医学版）》2021年第11期1187-1194,共8页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(31800774)。

摘　　要：目的:沙眼衣原体(Chlamydia trachomatis,Ct)泌尿生殖道感染引起输卵管积水和纤维化的机制尚不完全清楚。肠道微生物群除引起肠道疾病外,还与心脑血管疾病、肝硬化、呼吸道感染、多囊卵巢综合征、子宫内膜异位和细菌性阴道炎等肠外疾病的发生、发展密切相关。鼠李糖乳杆菌GG(Lactobacillus rhamnosus GG,LGG)是一种被广泛研究和应用的肠道益生菌,其益处包括治疗胃肠道疾病和调节机体免疫,它还可以缓解过敏反应和腹泻,并抑制各种呼吸道疾病和泌尿生殖系统病原体所致的疾病。本研究以致病性和Ct高度相似的鼠衣原体(Chlamydia muridarium,Cm)感染小鼠作为动物模型,初步探讨LGG对小鼠Cm上生殖道感染的调节作用及机制,为了解Ct泌尿生殖道感染的致病机制提供实验依据,并为Ct感染的治疗提供新的思路。方法:将6周龄C57BL/6J雌性小鼠分为实验组和对照组,其中实验组小鼠口服5×10^(8)菌落形成单位的LGG 19 d,对照组小鼠口服PBS。在两组小鼠口服LGG或PBS的第9天皮下注射2.5 mg孕酮,第14天经阴道感染1×10^(5)包涵体形成单位的Cm。小鼠感染Cm后,每周取阴道拭子和直肠拭子,将拭子系列稀释后接种HeLa细胞,24 h后进行间接免疫荧光染色,在显微镜下计数衣原体包涵体。于Cm感染后第14天和第63天分别处死小鼠,分离上、下生殖道,将组织匀浆接种HeLa细胞培养24 h后,计数两组小鼠双侧子宫角、输卵管卵巢及宫颈阴道组织中的Cm载量;用流式细胞术检测Cm感染后第14天小鼠脾T淋巴细胞胞内IFN-γ、IL-5和IL-17的分泌;观察感染后第63天小鼠双侧子宫角和输卵管的病理损伤,并将生殖道各部分进行病理切片和HE染色,评价输卵管管腔扩张和炎性细胞浸润程度;采用间接ELISA检测Cm感染后第14天和第63天小鼠血清特异性IgM和IgG水平。结果:Cm经阴道感染小鼠后,两组小鼠衣原体在生殖道的清除速度、感染�Objective:Chlamydia trachomatis is a pathogen which can cause hydrosalpinx and tubal fibrosis when infecting the urogenital tract.However,the mechanism is still not clear.There is growing evidence that the gut microbiota is associated with the pathogenesis of both intestinal and extra-intestinal disorders,such as cardiovascular disease,hepatocirrhosis,allergy,respiratory tract infection,polycystic ovary syndrome,endometriosis,and bacterial vaginitis.Lactobacillus rhamnosus GG(LGG)is one of the most extensively studied and widely used probiotic bacteria,the benefits of LGG including the treatment in gastrointestinal disorders and immunomodulation are well demonstrated,and it can also alleviate hypersensitivity reaction and diarrhoea,inhibit a variety of respiratory and urogenital diseases.Chlamydia muridarium(Cm)infection is a good model for the study on human Chlamydia pathogenicity in genitourinary tract.The mice infected with Cm were used as animal models to preliminarily explore the mechanism for the effect of LGG on upper reproductive tract infection in the mice,and to provide experimental basis for the pathogenesis of Chlamydia trachomatis genitourinary tract infection and the new idea for the treatment of Chlamydia trachomatis infection.Methods:Five to six weeks-old C57BL/6J mice were divided into 2 groups:An experimental group and a control group.The experimental group were administrated with 5×10^(8) colony forming units(CFU)LGG for 19 consecutive days,while the control group were feed PBS.The mice in the 2 group were subcutaneously injected with 2.5 mg progesterone on Day 9 and infected with 1×10^(5) inclusion body forming unit of Cm via the vaginal tract on Day 14.Vaginal and rectal swabs were taken every 7 days to infect HeLa cells for 24 hours,then the indirect immunofluorescence assay was used and the number of inclusion bodies of Chlamydia were calculated.Mice were euthanized on Day 14 and Day 63 after Cm inoculation,the vaginal tracts were dissected,and the tissue homogenates were prepared to cul

关 键 词：鼠李糖乳杆菌GG 鼠衣原体 输卵管积水 白细胞介素-17 

分 类 号：R691.3[医药卫生—泌尿科学]