子宮內膜異位症是影響生殖年齡約2-10%婦女常見的疾病，它主要牽涉月經的逆行到腹膜腔，但是造成子宮內膜異位症發展的關鍵性因素之一是免疫系統的改變或功能不良。巨噬球細胞已經被報導認為與子宮內膜異位症的嚴重程度有高度地相關性，從子宮內膜異位症病人分離的腹膜腔巨噬球發現有強烈地細胞動力素製造的能力但是其吞噬能力不足。巨噬球是腹膜腔中細胞動力素主要的製造者，它產生包括細胞介素(IL)-1b、IL-6和腫瘤壞疽因子- alpha。它們可能影響異位子宮內膜植入細胞的建立與增殖而形成子宮內膜異位症，並且回頭促進巨噬球分泌更多細胞動力素，進而加速子宮內膜異位症的形成。腹膜腔中巨噬球也表現瘦素的接受器，藉由瘦素的調節影響其吞噬能力；此外類固醇、前列腺素及血管新生的因子也會影響子宮內膜異位症的形成。本研究的主要目的首先在分析受到IL-1b影響的因素，我們發現子宮內膜異位症患者的腹膜腔巨噬球細胞表現COX-2的能力明顯增加，而且與腹膜腔巨噬球細胞的活化與腹腔液中前列腺素的增加有關。在沒有子宮內膜異位症患者的腹膜腔巨噬球細胞原本只產生極少量的COX-2，接受IL-1b刺激後COX-2以及前列腺素的表現增加；相反地有子宮內膜異位症的患者原本腹膜腔巨噬球細胞就已經表現極明顯的COX-2，但是在接受IL-1b刺激後COX-2增加的表現卻不明顯。另外在異位的子宮內膜基質細胞也有明顯COX-2的表現，但是與腹腔液中巨噬球細胞不一樣的地方是異位的子宮內膜在接受IL-1b刺激後COX-2的表現十分敏感，和正常位置的子宮內膜在接受 IL-1b刺激後增加的COX-2量相比較至少達100倍以上。接著我們希望找出腹腔液中Leptin的來源，我們發現腹腔液中巨噬球細胞並不會產生Leptin，但是有其接受器的存在，然而子宮內膜異位症患者腹腔液巨噬球細胞在Leptin刺激後與控制組病人相比COX-2的表現量一樣，無法使其表現更多COX-2；而子宮內膜異位患者的腹腔液中Leptin的增加是由異位的子宮內膜產生，而Leptin接受器在異位的子宮內膜的表現則是與Leptin的表現和疾病的嚴重程度成反比；異位的子宮內膜基質細胞在Leptin的刺激下會增加Leptin本身的表現，並抑制Leptin接受器的表現。因此我們認為腹腔液中巨噬球細胞以及異位的子宮內膜症病灶與正常位置的子宮內膜生化代謝的本質反應是不一樣的，而腹腔中局部內分泌環境尤其是腹腔液中巨噬球細胞的變化可以支撐異位子宮內膜的生長而存活下來，並且使得子宮內膜症更加惡化。

　Endometriosis is a common disease that affects 2-10% of women in the reproductive age. Alteration/dysfunction of immune system is a critical factor leading to the development of endometriosis. Functional defect in macrophage has been reported to highly associate with the severity of endometriosis. Peritoneal fluid of women with endometriosis, that contains various cytokines, prostanoids, growth factors and angiogenic factors, is involved in the pathogenesis of endometriosis, probably through affecting the functions of macrophage. Moreover, peritoneal macrophages isolated from patients with endometriosis secreted more cytokines, including interleukin (IL)-1b, IL-6, and tumor necrosis factor- alpha, but had poor phagocytotic capability than those from disease-free women. Macrophage is also a direct target of leptin, which is overexpressed in peritoneal fluid of patients with endometriosis. First, we try to find the targets of IL-1b. The expression of COX-2 was significantly increased in ectopic endometriotic tissue and peritoneal macrophages from women with endometriosis. Treatment of IL-1b increased the COX-2 expression in peritoneal macrophages of disease-free women, but failed to affect this gene in those cells of patients with endometriosis. Contrast to macrophages, ectopic endometriotic stromal cells were sensitive to IL-1b treatment. Secondly, we try to find which cells produce leptin, and can leptin modulate peritoneal macrophages? The same as the response in disease-free women, leptin had no substantial effect on COX-2 expression in peritoneal macrophages of patients with endometriosis. Ectopic endometriotic stromal cells showed increased leptin and decreased leptin receptor expression, which were in association with the severity of endometriosis. Differential expression of leptin and its receptor was noted in eutopic and ectopic stromal cells. Leptin also demonstrated receptor down-regulation and autoamplification effect in ectopic endometriotic stromal cells. In conclusion, peritoneal macrophage and stromal tissue presented in normal person and patients with endometriosis are biochemically different. These differences allow us to determine the molecular mechanism of peritoneal macrophage in the formation of endometriosis, and support the hypothesis that the local change of peritoneal microenvironment, especially in macrophage of peritoneal fluid, may contribute to the development and progression of this disease.

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