纤维细胞和前列腺素E_2在甲状腺相关眼病发病机制中的作用

The Role of fibrocytes and prostaglandin E_2 in the Pathogenesis of Thyroid Associated Ophthalmolopathy

目的探讨纤维细胞和前列腺素E2在甲状腺相关眼病(TAO)发病机制中的作用。方法 10例正常对照者,8例Graves病(GD)无眼病患者和11例TAO患者分别进行泪液PGE2、血清IL-1水平的检测以及血液纤维细胞的培养,并观察炎性刺激对纤维细胞释放PGE2的影响。结果泪液PGE2的浓度:TAO组患者较对照组显著增高,而GD无眼病组患者较对照组无显著差异;IL-1的血清浓度:相对正常对照组,TAO组和GD无眼病组患者均有显著升高,但TAO组和GD无眼病组患者之间并无显著差异;血液中纤维细胞的增殖水平:在TAO组患者较对照组显著增高,而GD无眼病组患者较对照组无显著差异;在离体实验中,IL-1显著提高纤维细胞PGE2的释放。结论 TAO中泪液PGE2的浓度和血液纤维细胞活性增加。在TAO中眶内组织肿胀和循环障碍可以刺激炎性因子释放,从而增加纤维细胞的浸润并增加PGE2的释放,而PGE2可以通过增加血管通透性而促使眶内组织水肿而进一步加重TAO。

Objective To investigate the contributions of fibrocytes and prostaglandin E2 in the pathogenesis of Thyroid associated ophthalmolopathy. Methods Study included 10 healthy subjects（ control group）,8 patients with Graves＇ disease（GD group） with no ophthalmopathy,and 11 patients with Graves＇ ophthalmopathy（ TAO group）. Tear PGE2 level,plasma IL-1 level,and circulating fibrocytes were obtained and compared between the groups. The fibrocytederived PGE2 was measured before and after administration of exogenous IL-1. Results GD patients and TAO patients exhibited increased plasma IL-1b compared to healthy subjects,while tear PGE2 levels and fibrocyte count were increased only in TAO patients. IL-1 treatment increased production of fibrocyte-derived PGE2. Conclusion The enlargement of orbital（fat and connective） tissue and resultant impaired local tissue perfusion may further drive local inflammatory responses and increase the production of PGE2. Accumulation of PGE2 then in turn increases capillary permeability and exacerbates orbital tissue edema and local inflammation. PGE2 released from local fibrocyte and /or other immune cells in response to local inflammatory stimuli is responsible for the pathological development of TAO.