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Analysis on tyrosinekinase receptor expression and tubal infertility

酪氨酸激酶受体表达与输卵管性不孕的分析

基本信息

批准号：
10671555
负责人：
ISHIMARU Tadayuki
金额：
$ 2.37万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671555/
关键词：
Oviduct infertility menstruation Ischemia-reperfusion Apoptosis Hepatocyte Growthfactor Nitric oxide TNFalfa チロシンキナーゼ

项目摘要

(study1) We analyzed histological and physiological changes in the rabbit oviduct at various time-points from 30 min to 14 day after ligation of both ends of oviduct. In the first 3days, the blood flow decreased, and TUNEL positive epithelial cells and NO level in the oviduct fluid increased. L-NAME injection reduced NO level and the accumulation of fluid. However, L-NAME increased TUNEL positive smooth muscle cells. These results indicated that the rapid increase in NO level after ligation may play a major role in the tissue injury and remodeling in rabbit oviduct. (study2) We established a uterine ischemia-reperfusion model in mice to investigate the pathological changes in the uterus and oviduct. Ischemia induced apoptosis in endometrium and oviduct. The pathological features similar to those seen in the human endometrium during menstruation. The expression levels of TNF α mRNAs in uterus increased after reperfusion. Apoptosis decreased in TNF-R p55-deficient mice, confirming the important role of TNF α in injury-induced apoptosis. Our model seems suitable for investigating human menstruation and tubal infertility. (study3) We analyzed fertilization and embryonal development with mouse uterine ischemic reperfusion model. In this model, the fertilization rate and embryonal development decreased. However, it was increased after injection of superoxide dismutase. This suggest that oxidative stress is the important factor in embryonal development. This model is useful in study of tubal infertility. (study4) We analyzed tyrosine kinase receptor profiles of mouse normal oviduct and ischemic oviduct. Using degenerated primer RT-PCR, the most characteristic receptor was c-met. C-met was expressed in mouse oviduct after ischemia reperfusion in mRNA and immunohistochemistry. After injection of anti c-met antibody, oviduct regeneration after ischemia was decreased. This suggest that c-met and hepatocyte growth factor was important in the oviduct regeneration.

（研究一）对家兔输卵管两端结扎后30 min ~ 14 d的不同时间点进行组织学和生理学观察。术后3d，输卵管血流减少，输卵管液中TUNEL阳性上皮细胞增多，NO水平升高。注射L-NAME可降低NO水平和液体积聚。而L-NAME可增加TUNEL阳性平滑肌细胞。提示结扎后NO水平的迅速升高可能在输卵管组织损伤和重塑中起重要作用。（研究二）建立小鼠子宫缺血再灌注模型，观察子宫和输卵管的病理变化。缺血诱导子宫内膜和输卵管细胞凋亡。其病理特征与月经期子宫内膜相似。子宫再灌注后TNF α mRNA表达水平升高。TNF-R p55缺陷小鼠的细胞凋亡减少，证实了TNF α在损伤诱导的细胞凋亡中的重要作用。我们的模型似乎适合调查人类月经和输卵管不孕症。（研究三）采用小鼠子宫缺血再灌注模型，分析受精和胚胎发育情况。在这种模式下，受精率和胚胎发育下降。而注射超氧化物歧化酶后，其含量增加。这表明氧化应激是影响胚胎发育的重要因素。该模型可用于输卵管性不孕症的研究。（研究4）分析小鼠正常输卵管和缺血输卵管的酪氨酸激酶受体谱。用简并引物RT-PCR检测，最具特征性的受体是c-met。在mRNA和免疫组化上，缺血再灌注后小鼠输卵管组织中C-met有表达。注射抗c-met抗体后，缺血后输卵管再生减少。提示c-met和肝细胞生长因子在输卵管再生中起重要作用。