2010-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/645177摘要：卵巢過度刺激症侯群(ovarian hyperstimulation syndrome，OHSS)是一種排卵刺激可能產生的副作用，臨床症狀包括明顯的卵巢腫大及腹水等現象。在先前的研究中我們發現OHSS 患者的卵巢濾泡液及腹水中均含有大量發炎反應分子，最近臨床文獻資料也顯示卵巢過度刺激情況下病人血清中發炎反應指標CRP 值會上升且其數值高低與卵巢過度刺激症侯群的發生相關。我們正以體外細胞培養模式，利用HCG 及LPA(lysophosphatidic acid)等，刺激人類黃體化顆粒細胞的反應，探討VEGF、IL-8、TNF-α等之分泌對於血管內皮細胞之作用。而本研究從另一角度、及動物模式，來探討發炎細胞及分子於OHSS 的角色。此外，我們比較免疫不全與免疫完整的小鼠所進行之卵巢過度刺激的研究結果顯示，兩種品系小鼠在接受卵子成熟與促進排卵的藥物後，卵巢腫大的程度並無差異。然而卵巢過度刺激會明顯改變免疫完整小鼠腹膜血管通透性，但此效應在免疫不全小鼠腹膜並不明顯。因此，在本研究中我們主要將探討免疫細胞在卵巢過度刺激症中的角色及其作用機轉，在三年期的計畫中，第一年的研究目標為釐清何種免疫細胞與小鼠腹膜血管通透性有關。第二年的研究目標為釐清免疫細胞放出的何種分子與小鼠腹膜血管通透性有關。第三年的研究目標為探討針對特殊免疫細胞或特殊分子之標靶治療在卵巢過度刺激症的應用潛力。近年來生殖醫學已成我國之重點，卵巢刺激在生殖醫學的應用相當普遍，臨床上OHSS 的產生嚴重時甚至有生命危險，有鑑於此，釐清OHSS 的產生機轉確實為生殖醫學發展上重要之課題。<br> Abstract: Ovarian hyperstimulation syndrome (OHSS) is a potential complication of ovarianstimulation. A critical condition develops with massive ascites or pleural effusion,hemoconcentration and thromboembolism that can be life-threatening. The underlying causeis an increase in the capillary permeability of ovaries and mesothelial surfaces withextravasation of fluid. In our previously study, we found that large amounts of inflammatorycytokines were found in the follicular fluid and ascites from OHSS patients. There are alsoclinical evidences showed that the inflammatory index CRP value was correlated with OHSS.Now we are studying the effect of HCG and lysophosphatidic acid (LPA) on granulosa-luteincells, and investigating the mechanisms of how they regulated VEGF, IL-8 or TNF-alphaexpression that may led to increased endothelial permeability of OHSS. On the other hand, wecompared the phenotypes of OHSS between the severe combined immunodeficiencies (SCID)mouse and normal healthy (wild type) mouse, we found that the enlargement of ovaries wassimilar in both mouse strains, however, the increasing effect of the peritoneal capillarypermeability was only found in the wild type strain. The above finding may imply the role ofimmune system in OHSS. In the three years project, we will mainly focus on the role ofimmune cells and its related inflammatory cytokines in OHSS. In the first year, the aim is tofind out the role of different immune cells in peritoneal capillary permeability change. Theaim of the second year is to verify the key factors from the certain immune cell thatmodulated the capillary permeability. In the third year, we will design the therapeuticstrategies that base on the molecular mechanisms. The investigation of therapeutic strategieswill be performed in vitro and in mouse model. Nowadays, the usage of controlled ovarianhyperstimulation plays important role in the human reproduction medicine. We expect thatthis study would be useful to realize the molecular mechanisms and work out medicines fortarget therapy of OHSS.卵巢過度刺激症侯群免疫細胞血管通透性標靶治療動物模式ovarian hyperstimulation syndromeimmune cellsendothelial permeabilitytargeting therapymouse model