Seenan Vaishnavi, Hsu Che-Fang, Subramani Kanchana, Chen Pao-Chu, Ding Dah-Ching, Chu Tang-Yuan
Center for Prevention and Therapy of Gynecological Cancers, Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan, ROC.
Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan, ROC.
iScience. 2024 Apr 18;27(6):109788. doi: 10.1016/j.isci.2024.109788. eCollection 2024 Jun 21.
Postoperative adhesions show a higher occurrence in females aged 16-60, especially after pelvic surgeries. This study explores the role of ovulation in adhesion formation in mice. Ovarian surgery in mice with normal- or super-ovulation led to pronounced adhesions, whereas ovulation-defective -KO mice showed minimal adhesions. Specifically, exposure to ovulatory follicular fluid (FF) markedly increased the adhesion. The hazardous exposure time window was one day before to 2.5 days after the surgery. Mechanistically, early FF exposure triggered adhesions via the blood coagulation cascade, while later exposure relied on the HGF/cMET signaling pathway. Prophylactic administration of a thrombin inhibitor pre-operatively or a cMET inhibitor postoperatively effectively mitigated FF-induced adhesions, while COX inhibitor treatment exhibited no discernible effect. These findings underscore ovulation as a pivotal factor in the development of pelvic wound adhesions and advocate for targeted preventive strategies such as c-MET inhibition, scheduling surgeries outside the ovulatory period, or employing oral contraceptive measures.
术后粘连在16至60岁的女性中发生率较高,尤其是在盆腔手术后。本研究探讨排卵在小鼠粘连形成中的作用。对正常排卵或超排卵的小鼠进行卵巢手术会导致明显的粘连,而排卵缺陷的敲除小鼠则显示出最小程度的粘连。具体而言,暴露于排卵卵泡液(FF)会显著增加粘连。危险暴露时间窗口为手术前一天至手术后2.5天。从机制上讲,早期FF暴露通过凝血级联反应引发粘连,而后期暴露则依赖于HGF/cMET信号通路。术前预防性给予凝血酶抑制剂或术后给予cMET抑制剂可有效减轻FF诱导的粘连,而COX抑制剂治疗则无明显效果。这些发现强调排卵是盆腔伤口粘连发展的关键因素,并提倡采取针对性的预防策略,如抑制c-MET、在非排卵期安排手术或采取口服避孕措施。