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：释放有或没有促性腺激素的抗生素治疗激素激动剂（GNRHA）可能会降低子宫内感染，从而导致内膜异痛女性的组织炎症，血管生成和慢性内膜炎的组织炎症，细胞增殖，血管生成和慢性内膜炎的发生。我们进行了一项前瞻性非随机观察研究，并收集了来自53例子宫内膜异位症女性的子宫内膜和子宫内膜含量样本，在手术过程中没有子宫内膜异位症。手术前，将这两组患者用左氧氟沙星（LVFX，500mg一次）或GNRHA（1.88 mg/im）治疗。通过靶向16S rRNA基因的V5-V6区域的细菌的宽范围PCR扩增来分析子宫内膜样品。使用各自的靶抗体进行免疫组织化学。 16S rDNA元基因组测定法表明，与未经治疗的组相比，用LVFX或GNRHA+LVFX处理显着降低了主要细菌属的某些成分。 GNRHA+LVFX治疗后，慢性子宫内膜炎的发生显着降低。 CD68染色的巨噬细胞浸润，KI-67染色的细胞增殖和CD31染色的微Vessel密度在内部测室和子宫内膜异位损伤中发现，并在子宫内膜异位症的形态外观中提高了组织学改善。这些发现表明，具有或没有GNRHA的广谱抗生素的临床应用可能有效地改善人子宫内膜异位症中的子宫感染。