载Apelin-13缓释微囊的新型生物支架促兔输卵管再通的初步研究

Preliminary study on a novel biological scaffold loaded with Apelin-13 sustained-release microcapsules for promoting fallopian tube recanalization in rabbits

目的:输卵管炎性不孕症严重危害女性自然生育功能,临床迫切需求的真正意义上的输卵管再通包括病变输卵管解剖和功能的修复两方面,目前尚无有效的治疗方案。本研究旨在从这两方面探讨促进输卵管修复再通的方法。方法:制备Apelin-13缓释微囊和聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]三维生物支架,检测生物支架的基本特性及体内降解情况(质量损失率),微囊的体外释药(累积释药率)、体内释药(Apelin-13血药浓度)及体外降解(降解率)情况。将Apelin-13微囊(微囊组)/载Apelin-13缓释微囊的PLGA三维生物支架(支架微囊组)注入/置入慢性输卵管炎新西兰兔模型的输卵管,观察和比较对照组、模型组、微囊组和支架微囊组术后输卵管的通畅情况、镜下结构、雌激素受体和孕激素受体的阳性表达情况。结果:术后第4周时PLGA三维生物支架的质量损失率为98.66%,微囊的体外降解率为70.58%,Apelin-13缓释微囊30 d体外累计释药率达98.68%,Apelin-13血药浓度在5 d内达到峰值,并在25 d内保持稳定。与模型组和微囊组相比,支架微囊组术后输卵管管腔内炎症反应轻,输卵管通畅率高,雌激素受体和孕激素受体的表达水平高(均P<0.05),支架微囊组的各项指标接近对照组。结论:载Apelin-13缓释微囊的PLGA三维生物支架可全面修复输卵管的解剖结构和生理功能,有望真正有效实现炎性输卵管再通。

Objective: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.Methods: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.Results: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 microspheresgenerated 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 P<0.05).The indicators of the scaffold-microsphere group were close to those of the control group.Conclusion: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.