Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Obstetrics and Gynecology, Kuo General Hospital, Tainan, Taiwan.
Department of Obstetrics and Gynecology, An-An Women and Children Clinic, Tainan, Taiwan.
Taiwan J Obstet Gynecol. 2021 Jul;60(4):711-717. doi: 10.1016/j.tjog.2021.05.022.
Endometriosis is a bothersome disease affected women worldwide, the mechanism of disease development is still under investigation. Several inflammatory responses after clinical hyaluronic acid (HA) use were reported. Cyclooxygenase (COX)-2 mediated inflammation pathway is involved in the pathogenesis of endometriosis. Thus, we tried to investigate the inflammatory role of hyaluronic acid in endometriosis.
Peritoneal fluid was collected in endometriosis and disease-free patients for the measurement of HA. Endometriotic stromal cells were treated with IL-1β and HA and expression of COX-2 was evaluated. Mice model of endometriosis was established and treated with fluid or gel form of HA. Endometriotic lesion size and weight were recorded and level of COX-2 was evaluated by immunohistochemistry staining.
The level of HA in the peritoneal fluid had no statistically significant difference between normal, early and advanced stage endometriosis patients. The overexpression of COX-2 protein was detected when treating endometriotic stromal cell with HA in the presence of IL-1β (P < 0.001). The endometriotic lesion size was reduced in mice model when treated with higher concentration gel form HA. It further showed less proportion of strong COX-2 expression compare of gel form HA to fluid form treatment in COX-2 expression score of endometriosis lesion.
Both proinflammatory evidence, elevated COX-2 expression, and anti-inflammatory result, reduced endometriosis lesion size and COX-2 expression score, were noted in our study after treating HA in in vivo and in vitro models. We hypothesized it is possible that HA may induce an acute proinflammatory response followed by chronic anti-inflammatory reaction in the formation of endometriosis.
子宫内膜异位症是一种影响全球女性的令人困扰的疾病,其发病机制仍在研究中。有报道称,在临床使用透明质酸(HA)后会发生几种炎症反应。环氧化酶(COX)-2 介导的炎症通路参与了子宫内膜异位症的发病机制。因此,我们试图研究透明质酸在子宫内膜异位症中的炎症作用。
收集子宫内膜异位症和无疾病患者的腹腔液以测量 HA。用 IL-1β 和 HA 处理子宫内膜异位症基质细胞,并评估 COX-2 的表达。建立子宫内膜异位症小鼠模型,并以 HA 的液体或凝胶形式进行治疗。记录子宫内膜异位症病变的大小和重量,并通过免疫组织化学染色评估 COX-2 水平。
正常、早期和晚期子宫内膜异位症患者腹腔液中的 HA 水平无统计学差异。当子宫内膜异位症基质细胞在 IL-1β 存在下用 HA 处理时,检测到 COX-2 蛋白过表达(P<0.001)。在使用较高浓度凝胶形式 HA 治疗的小鼠模型中,子宫内膜异位症病变的大小减小。与凝胶形式 HA 相比,在 COX-2 表达评分中,凝胶形式 HA 处理的子宫内膜异位症病变中 COX-2 表达的比例较低。
在体内和体外模型中用 HA 治疗后,我们观察到了两种促炎证据,即 COX-2 表达升高,以及抗炎结果,即子宫内膜异位症病变的大小和 COX-2 表达评分降低。我们推测 HA 可能在子宫内膜异位症的形成过程中引起急性促炎反应,随后是慢性抗炎反应。