Analysis of pain related gene expression in endometriosis and endometriosis related pelvic pain

子宫内膜异位症及子宫内膜异位症相关盆腔疼痛疼痛相关基因表达分析

• 批准号: 18613017
• 负责人: ASADA Hironori
• 金额: $ 2.61万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18613017/
• 关键词: endometriosis; NGF; TrkA; p75NTR; TrkA

Endometriosis is a poorly understood, estradiol-dependent condition associated with severe pelvic pains and defined by vascularized endometrial growths outside the uterus. However, the mechanisms by which pain is generated remain unknown. The broad scope of neurotrophin action is well documented in the case of nerve growth factor (NGF) and its effect on nociceptors and nociception. It was reported that NGF is up-regulated after inflammatory injury and administration of exogenous NGF either systemically or in the skin causes thermal hyperalgesia. We examined NGF, TrkA receptor and p75 receptor expression in the endometriotic lesion and normal endometrium by means of immunohistochemistry, RT-PCR and Western blot. Endometrial cyst wall, adenomyotic lesions, peritoneal endometriotic lesions and normal endometrium were prepared (n=19, 4, 8 and 8, respectively). NGF expression was significantly stronger in peritoneal endometriosis, endometriotic cyst, and adenomotic lesions than in normal endometrium. NGF expression was the most stronger in peritoneal lesions. Although the low affinity neurotrophin receptor (p75NTR) was detected in the endometriotic lesions, high affinity NGF receptor (TrkA) was not detectied in the endometriotic lesions. The levels of NGF in peritoneal fluid were also measured to compare the concentration in women who have endometriosis and in women without endometriosis. NGF was detected in 45% cases. 5 of the 18 control samples (28%) was positive. Of the 46 samples of endometriosis patients, 24 was positive for NGF (52%). These results suggest a role of NGF in the progression of endometriosis. The pain and hyperalgesia in endometriosis may be related with the expression of NGF. The expression of the NGF- p75NTR could explain hyperalgesia in endometriosis.

子宫内膜异位症是一种鲜为人知的，依赖雌二醇的疾病，与严重的盆腔疼痛有关，并定义为子宫外血管化的子宫内膜生长。然而，疼痛产生的机制仍然未知。神经生长因子（NGF）及其对伤害感受器和伤害感受的作用的广泛范围的神经营养作用是有据可查的。有研究表明，炎症损伤后NGF表达上调，全身或皮肤给予外源性NGF可引起热痛觉过敏。采用免疫组化、RT-PCR和Western blot方法检测NGF、TrkA受体和p75受体在子宫内膜异位症病变和正常子宫内膜中的表达。分别取子宫内膜囊肿壁19例、子宫腺肌病4例、腹膜炎8例和正常子宫内膜8例。NGF在腹膜子宫内膜异位症、子宫内膜异位囊肿和子宫内膜异位病变中的表达明显强于正常子宫内膜。NGF在腹膜病变中表达最强。低亲和力神经营养素受体（p75 NTR）在病变组织中表达，而高亲和力神经生长因子受体（TrkA）在病变组织中未表达。还测量了腹腔液中NGF的水平，以比较患有子宫内膜异位症的妇女和没有子宫内膜异位症的妇女的浓度。45%的病例检测到NGF。18份对照样品中有5份（28%）为阳性。在46例子宫内膜异位症患者中，24例（52%）NGF阳性。这些结果表明，神经生长因子在子宫内膜异位症的进展中的作用。子宫内膜异位症的疼痛和痛觉过敏可能与神经生长因子的表达有关。NGF-p75 NTR的表达可以解释子宫内膜异位症的痛觉过敏。

项目成果

Side population in human uterine myometrium displays phynotypic and functional characteristics of myometrial stem cells

人子宫肌层中的侧群显示出子宫肌层干细胞的表型和功能特征

• 发表时间: 2007
• 期刊: Proc Natl Acad Sci USA 104
• 作者: Ono M;Maruyama T;Masuda H;Kajitani T;Nagashima T;Arase T;Ito M;Ohta K;Uchida H;Asada H;Yoshimura Y;Okano H;Matsuzaki Y
• 通讯作者: Matsuzaki Y

【妊孕能温存のための内視鏡手術】子宮腺筋症に対する内視鏡手術

[保留生育能力的内镜手术] 子宫腺肌症的内镜手术

• 发表时间: 2006
• 期刊: 産婦人科の世界 58・4
• 作者: 浅田弘法;梶谷宇;丸山哲生 他
• 通讯作者: 丸山哲生 他

子宮筋腫,別冊日本臨床

子宫肌瘤，单独的日本临床版

• 发表时间: 2006
• 作者: 丸山 哲夫、浅田 弘法;ほか
• 通讯作者: ほか

Expression and localization of nerve growoth factor in the endometriotic and adenomyotic lesions

神经生长因子在子宫内膜异位症和子宫腺肌病病变中的表达和定位

• 发表时间: 2007
• 作者: Kajitani T;Maruyama T;Asada H;Uchida H;Masuda H;Nagashima T;Ono M;Arase T;Ohta K;Kagami M;Yoshimura Y
• 通讯作者: Yoshimura Y

Noninvasive and real-time assessment of reconstructed functional human endometrium in NOD/SCID/gammac null immunodeficient mice.

对 NOD/SCID/gamma 免疫缺陷小鼠重建功能性人类子宫内膜进行无创实时评估。

• 发表时间: 2007
• 期刊: Proc Natl Acad Sci U S A 104 (6)
• 作者: Masuda H;et al.
• 通讯作者: et al.