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子宮内膜症における子宮腔内細菌叢の同定と細菌環境が不妊医療に及ぼす影響

子宫内膜异位症子宫腔菌群鉴定及细菌环境对不孕不育医学的影响

基本信息

批准号：
18K09268
负责人：
カーンカレク
金额：
$ 2.75万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2018
资助国家：
日本
起止时间：
2018-04-01 至 2024-03-31
项目状态：
已结题

项目摘要

We examined the hypothesis that antibiotic treatment with and without gonadotropin releasing hormone agonist (GnRHa) may decrease intrauterine infection with consequent decrease in tissue inflammation, cell proliferation, angiogenesis and occurrence of chronic endometritis in women with endometriosis. We performed a prospective non-randomized observational study with collection of endometrial and endometriotic samples from 53 women with endometriosis and 47 women without endometriosis during surgery. These two groups of patients were treated with levofloxacin (LVFX, 500mg once per os) or GnRHa (1.88 mg/IM for 3 months) before surgery. Endometrial samples were analyzed by broad-range PCR amplification of bacteria targeting V5-V6 region of 16S rRNA gene. Immunohistochemistry was performed using respective target antibodies. 16S rDNA metagenome assay indicated that treatment with either LVFX or GnRHa+LVFX significantly decreased some components of major bacterial genera comparing to untreated group. Occurrence of chronic endometritis was significantly decreased after GnRHa+LVFX treatment. A significantly decreased CD68-stained macrophage infiltration, Ki-67-stained cell proliferation and CD31-stained micro-vessel density was found in endometria and endometriotic lesions with histology-proven improvement in the morphological appearance of endometriosis. These findings suggest that clinical application of a broad-spectrum antibiotic with or without GnRHa may be effective in improving uterine infection in human endometriosis.

我们研究了以下假设：在子宫内膜异位症患者中，使用或不使用促性腺激素释放激素激动剂（GnRHa）进行抗生素治疗可能会减少宫内感染，从而减少组织炎症、细胞增殖、血管生成和慢性子宫内膜炎的发生。我们进行了一项前瞻性非随机观察性研究，收集了53名子宫内膜异位症患者和47名非子宫内膜异位症患者手术期间的子宫内膜和子宫内膜异位症样本。两组患者术前均给予左氧氟沙星（LVFX，500 mg，1次/口）或GnRHa（1.88mg/IM，3个月）治疗。子宫内膜标本采用16 SrRNA基因V5-V6区细菌大范围PCR扩增进行分析。使用各自的靶抗体进行免疫组织化学。16 S rDNA宏基因组分析表明，与未处理组相比，LVFX或GnRHa+LVFX处理显著降低了主要细菌属的某些组分。GnRHa+LVFX治疗后慢性胃炎的发生率显著降低。CD 68染色的巨噬细胞浸润，Ki-67染色的细胞增殖和CD 31染色的微血管密度显着下降，发现在子宫内膜异位症和子宫内膜异位症病变与组织学证明的改善形态外观。这些结果表明，临床应用广谱抗生素与或不GnRHa可能是有效的，在改善子宫内膜异位症的子宫感染。