Health Management Center, Third Xiangya Hospital, Central South University, Changsha 410013.
Department of Gynecology, Third Xiangya Hospital, Central South University, Changsha 410013.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023;48(9):1304-1315. doi: 10.11817/j.issn.1672-7347.2023.230067.
Tubal factor infertility severely impairs the natural fertility of women, and there is for genuine tubal recanalization, including restoration of both the anatomy and function of the diseased fallopian tubes. Currently, there is no effective treatment available. This study aims to explore methods for promoting the repair and recanalization of fallopian tubes from these 2 aspects.
Apelin-13 sustained-release microspheres and poly (lactic-co-glycolic acid) (PLGA) three-dimensional (3D) biodegradable scaffolds were prepared. The basic characteristics and in vivo degradation (mass loss rate) of the biodegradable scaffolds were tested, along with the in vitro drug release (cumulative release rate), the in vivo drug release (Apelin-13 plasma concentration), and in vitro degradation (degradation rate) of the microspheres. The Apelin-13 microspheres (microsphere group)/PLGA 3D scaffolds loaded with Apelin-13 sustained-release microspheres (scaffold-microcapsule group) were injected/placed into the fallopian tubes of New Zealand rabbit of chronic salpingitis models. The patency, microscopic structure, and positive expression of estrogen receptor and progesterone receptor of the fallopian tubes in the control group, the model group, the microcapsule group, and the scaffold-microcapsule group was observed and compared.
At the 4th week post-operation, the mass loss rate of the PLGA 3D scaffolds, the degradation rate of the microspheres, and the Apelin-13 sustained-release microspheres-generated cumulative release rate in vitro over 30 days were 98.66%, 70.58%, and 98.68% respectively. The plasma concentration of Apelin-13 reached its peak within 5 days and remained stable for 25 days. Compared with the model and microsphere groups, the scaffold-microsphere group showed a milder inflammatory reaction within the tubal lumen, a higher rate of fallopian tube patency, and higher expression levels of estrogen and progesterone receptors (all <0.05). The indicators of the scaffold-microsphere group were close to those of the control group.
The PLGA 3D scaffolds loaded with Apelin-13 sustained-release microspheres can comprehensively repair the anatomical structure and physiological function of the fallopian tubes and hold promise for truly effective tubal recanalization.
输卵管因素不孕严重损害了女性的自然生育能力,真正的输卵管再通需要同时恢复病变输卵管的解剖结构和功能。目前尚无有效的治疗方法。本研究旨在从这两个方面探索促进输卵管修复和再通的方法。
制备阿普林-13 持续释放微球和聚乳酸-羟基乙酸共聚物(PLGA)三维(3D)可生物降解支架。测试了可生物降解支架的基本特性和体内降解(质量损失率)、体外药物释放(累积释放率)、微球的体内药物释放(阿普林-13 血浆浓度)和体外降解(降解率)。将阿普林-13 微球(微球组)/载有阿普林-13 持续释放微球的 PLGA 3D 支架(支架-微球组)注入/放置到慢性输卵管炎新西兰兔模型的输卵管中。观察和比较对照组、模型组、微球组和支架-微球组的输卵管通畅性、显微镜结构、雌激素受体和孕激素受体的阳性表达。
术后第 4 周,PLGA 3D 支架的质量损失率、微球的降解率以及体外 30 天内阿普林-13 持续释放微球产生的累积释放率分别为 98.66%、70.58%和 98.68%。阿普林-13 的血浆浓度在 5 天内达到峰值,25 天内保持稳定。与模型组和微球组相比,支架-微球组管腔内炎症反应较轻,输卵管通畅率较高,雌激素和孕激素受体表达水平较高(均<0.05)。支架-微球组的各项指标均接近对照组。
载有阿普林-13 持续释放微球的 PLGA 3D 支架可全面修复输卵管的解剖结构和生理功能,有望真正实现有效的输卵管再通。