Fujian Maternity and Child Health Hospital, Fujian Medical University, Fuzhou Fujian 350001, China.
Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China.
Reprod Biomed Online. 2021 Sep;43(3):379-393. doi: 10.1016/j.rbmo.2021.04.017. Epub 2021 Apr 29.
Can preoperative or perioperative intervention reduce the risk of recurrence of endometriosis caused by either incomplete excision or spillage and dissemination?
A mouse model of endometriosis recurrence caused by spillage and dissemination was first established using 24 female Balb/c mice. The spillage and dissemination model was used to test the efficacy of preoperative use of ketorolac, perioperative use of aprepitant and combined use of propranolol and andrographolide in a prospective, randomized mouse experiment involving 75 mice. The efficacy of these preoperative and perioperative interventions in a mouse recurrence model caused by incomplete excision was also tested using 72 mice. In all experiments, the baseline body weight and hotplate latency of all mice were measured and recorded before the induction of endometriosis, before the primary surgery and before sacrifice. In addition, all lesions were excised, weighed and processed for quantification and immunohistochemistry analysis of E-cadherin, α-SMA, VEGF, ADRB2 and putative markers of recurrence PR-B, p-p65, as well as Masson trichrome staining.
All interventions substantially and significantly suppressed the outgrowth of endometriotic lesions and reduced the risk of recurrence caused by either spillage and dissemination or incomplete excision (P = 0.0007 to 0.042). These interventions also significantly attenuated the generalized hyperalgesia, inhibited the staining of α-SMA, p-p65, VEGF and ADRB2 but increased staining of E-cadherin and PR-B, resulting in reduced fibrosis.
Given the excellent safety profiles of these drugs, these data strongly suggest that preoperative and perioperative intervention may potentially reduce the risk of endometriosis recurrence effectively.
术前或围手术期干预能否降低因不完全切除或溢出和播散导致的子宫内膜异位症复发的风险？
首先使用 24 只雌性 Balb/c 小鼠建立因溢出和播散导致的子宫内膜异位症复发的小鼠模型。使用溢出和播散模型，在涉及 75 只小鼠的前瞻性、随机小鼠实验中测试术前使用酮咯酸、围手术期使用阿瑞匹坦和联合使用普萘洛尔和穿心莲内酯的疗效。还使用 72 只小鼠测试这些术前和围手术期干预在因不完全切除导致的小鼠复发模型中的疗效。在所有实验中，在诱导子宫内膜异位症、初次手术前和处死前测量并记录所有小鼠的基线体重和热板潜伏期。此外，还切除、称重并处理所有病变，用于 E-cadherin、α-SMA、VEGF、ADRB2 和假定复发标志物 PR-B、p-p65 的定量和免疫组织化学分析，以及 Masson 三色染色。
所有干预措施均显著抑制子宫内膜异位症病变的生长，并降低因溢出和播散或不完全切除引起的复发风险（P=0.0007 至 0.042）。这些干预措施还显著减弱了全身痛觉过敏，抑制了 α-SMA、p-p65、VEGF 和 ADRB2 的染色，但增加了 E-cadherin 和 PR-B 的染色，导致纤维化减少。
鉴于这些药物的良好安全性，这些数据强烈表明术前和围手术期干预可能有效降低子宫内膜异位症复发的风险。
