四种新西兰大白兔宫腔粘连模型的建立与评价及其对子宫内膜容受性的影响

Establishment and evaluation of four models of intrauterine adhesion and its effects on endometrial receptivity in New Zealand white rabbits

目的探讨建立稳定有效且符合临床病理特征的宫腔粘连(intrauterne adhesion,IUA)实验动物模型及四种不同造模方法对子宫内膜容受性的影响。方法将雌性普通级新西兰大白兔随机分为5组,按照损伤方式的不同将其分为假手术组、机械损伤组、化学损伤组、热损伤组和机械损伤合并感染组,在术后4、7、14和28 d收集兔双侧子宫组织,观察两侧子宫内膜病理改变,使用苏木精-伊红(Hematoxylin-eosin,HE)染色和Masson染色分析两侧子宫内膜的厚度、腺体数目和纤维化面积比率,以评估粘连的严重程度;并通过生殖功能实验检测其妊娠率和子宫胚胎着床数目等生育功能方面的差异。结果病理组织学观察显示,造模后7和14 d,化学损伤组、机械感染双损伤组和热损伤组相比假手术组,其子宫内膜厚度和腺体数目均有下降(P<0.05),子宫内膜纤维化面积比增高(P<0.05),而机械损伤组差异无统计学意义(P>0.05)。造模后14 d,相比假手术组,化学损伤组妊娠率和子宫胚胎着床数目下降(P<0.05),热损伤组兔子宫胚胎着床数目下降更加明显(P<0.001)。造模后28 d,除热损伤组外其余三组基本恢复。结论总体而言,化学损伤造模法其雌兔子宫病理组织学变化与临床人类中重度IUA特征更为接近,可以作为一种有效的模拟人类中重度IUA模型的方法,进一步为深入研究IUA的发病机制及治疗提供基础。

Objective To explore the effects of four different modeling method on endometrial receptivity,and establish a stable and effective experimental animal model of intrauterine adhesion(IUA)with clinicopathological characteristics.Methods New Zealand white rabbits were randomly divided into 5 groups,according to different method of damage:chemical,infection,mechanical,thermal,and sham-operated(control)groups.Rabbit bilateral uterine tissue was collected 4,7,14 and 28 d after treatment,and pathological changes were examined on both sides of the endometrium,using hematoxylin-eosin and Masson staining analysis.The thickness and number of endometrial glands and fibrosis area ratios were determined to evaluate the severity of adhesions.Pregnancy rates and the number of embryo implantations were used to examine reproductive function.Results Histopathological observations showed that both endometrial thickness and the number of glands decreased in the chemical-injured and heat-injured groups compared with the control group 7 and 14 d after treatment(P<0.05),whereas the endometrial fibrosis area ratio was increased(P<0.05).There were no significant differences between the mechanical damage and control groups.At 14 d after modeling,the pregnancy rate and number of uterine embryo implantations decreased in the chemical compared with the control group(P<0.05),and the number of rabbit embryo implantations was significantly reduced(P<0.001)in the heatinjured compared with control group.After 28 d of modeling,the chemical,infection and mechanical groups had basically recovered,but not the heat damage group.Conclusions In general,the histopathological changes observed in rabbit uteri after chemical injury modeling were more similar to the characteristics of moderate and severe IUA in humans,indicating this approach may be used as an effective model to investigate moderate and severe human IUA,and provide a basis for future in-depth study of the pathogenesis and treatment of IUA.