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妇产科手术后宫腔粘连形成的局部肾素-血管紧张素系统分子机制:新的治疗策略。

Local renin-angiotensin system molecular mechanisms in intrauterine adhesions formation following gynecological operations, new strategy for novel treatment.

机构信息

Department of Obstetrics and Gynecology, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

J Obstet Gynaecol. 2022 Aug;42(6):1613-1618. doi: 10.1080/01443615.2022.2036972. Epub 2022 Mar 9.

Abstract

It has recently been proposed that local tissue renin-angiotensin system activation has a role in post-surgical adhesion. Intrauterine adhesions are scar tissues that form in the endometrial cavity causing the walls of the uterine to adhere together. Women, undergoing major gynecological surgery, are exposed to a high risk of adhesion formation. Post-operative uterine adhesion is associated with chronic pain and infertility that are important problems following post-operation uterine adhesion. A local renin-angiotensin system has been found in the organs of the female reproductive system, for example in the endometrium. Data about the physiological roles of local RAS in the gynecological tract are largely unknown, but dysfunctional local RAS in the endometrium may contribute to this pathological condition. Local AngII/AT1R may be over-activated after surgical injury or hypoxia leading to an up-regulation of the molecular mechanisms that may lead to a chronic immune response, oxidative stress, and increase the expression of fibrotic molecules like TGF-β to induce the risk of connective fibrotic tissues. Based on AngII/AT1R pathological potential to induce pelvic and uterine adhesions, using angiotensin receptor blockers could be a therapeutic strategy for the prevention and treatment of post-surgical adhesions.IMPACT STATEMENT Intrauterine adhesions are described as fibrotic scar tissues following gynecological surgeries. It's reported that 55-100% of women are at risk of intrauterine adhesion after gynecological surgeries. Injury to tissues and hypoxia during the surgery, promote molecular mechanisms to contribute post-surgical adhesion. Recently evidence supports the existence of renin-angiotensin system components in the gynecological tract. Abnormal expression of local angiotensin II and AT1R in uterus tissue following gynecological surgeries up-regulate molecular mechanisms to induce post-operative adhesions. Recently there has been an increased focus on the role of the local renin-angiotensin system in organ fibrosis. The results of this Mini-review article refer to the pathological roles of the local renin-angiotensin system in fibrotic bands formation after gynecological operations. Over-activation of local renin-angiotensin systems up-regulate molecular mechanisms such as inflammation and the TGF-β1 signalling pathway. TGF-β as a profibrotic molecule strongly induces the expression of some fibrotic molecules such as PAI and TIMP to increase the risk of intrauterine adhesions. According to the biological roles of local renin-angiotensin system and AT1R following injuries to develop post-operative adhesion, the administration of ARBs may be considered as a new therapeutic strategy for the prevention of IUA.

摘要

最近有人提出,局部组织肾素-血管紧张素系统的激活在术后粘连中起作用。宫腔粘连是在子宫内膜腔中形成的疤痕组织,导致子宫壁粘连在一起。接受重大妇科手术的女性有很高的粘连形成风险。术后子宫粘连与慢性疼痛和不孕有关,这是术后子宫粘连的重要问题。已经在女性生殖系统的器官中发现了局部肾素-血管紧张素系统,例如在内膜中。关于妇科生殖道局部 RAS 的生理作用的数据在很大程度上尚不清楚,但子宫内膜局部 RAS 功能障碍可能导致这种病理状态。手术损伤或缺氧后,局部 AngII/AT1R 可能过度激活,导致可能导致慢性免疫反应、氧化应激和增加纤维化分子如 TGF-β表达的分子机制上调,从而增加结缔组织纤维化的风险。基于 AngII/AT1R 诱导盆腔和子宫粘连的病理潜力,使用血管紧张素受体阻滞剂可能是预防和治疗术后粘连的一种治疗策略。

宫内粘连被描述为妇科手术后的纤维疤痕组织。据报道,55-100%的女性在妇科手术后有发生宫内粘连的风险。手术过程中的组织损伤和缺氧促进了分子机制的形成,导致了术后粘连。最近的证据支持肾素-血管紧张素系统成分在妇科生殖道中的存在。妇科手术后子宫组织中局部血管紧张素 II 和 AT1R 的异常表达上调了诱导术后粘连的分子机制。最近,人们越来越关注局部肾素-血管紧张素系统在器官纤维化中的作用。这篇迷你综述文章的结果涉及局部肾素-血管紧张素系统在妇科手术后纤维带形成中的病理作用。局部肾素-血管紧张素系统的过度激活上调了炎症和 TGF-β1 信号通路等分子机制。TGF-β作为一种促纤维化分子,强烈诱导一些纤维化分子如 PAI 和 TIMP 的表达,增加了宫内粘连的风险。根据局部肾素-血管紧张素系统和 AT1R 在损伤后的生物学作用,开发术后粘连,血管紧张素受体阻滞剂的给药可能被认为是预防 IUA 的一种新的治疗策略。

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