基于病因学的多重损伤法宫腔粘连大鼠模型的建立和评价

Establishment and Evaluation of the Intrauterin Adhesion Rat Model Fabricated with Etiological Multi-injury Factors

目的探讨模拟人类病因学多因素建立一种稳定可靠的宫腔粘连SD大鼠疾病模型,为进一步研究发病机制和临床干预做基础。方法48只雌性SD大鼠随机分为A组:宫腔损伤+感染(16只);B组:宫腔损伤+切除双侧卵巢的低雌激素状态(16只);C组:宫腔损伤+感染+低雌激素状态(16只);D组:对照组(16只)不做宫腔处理,分批于造模后第7、14、21和28天处死大鼠取出子宫,以美国生育协会(American Fertility Sociation,AFS)评分标准对子宫粘连范围及程度进行评价,HE和Masson染色观察子宫内膜组织病理变化,以造模后第28天为节点计数子宫内膜腺体数量和间质纤维化面积比率。结果四组间大鼠AFS评分和成模率差异均有统计学意义(P均<0.05),B、C组均高于A组和D组(P均<0.05);与D组相比,造模的三组大鼠在子宫内膜腺体数量上均有下降,内膜纤维化面积增加(P均<0.05);加入低雌激素的B、C组子宫内膜腺体数量少于A组、内膜纤维化面积高于A组(P均<0.05)。结论采用损伤、感染及低雌激素状态多重因素可以建立稳定的大鼠宫腔粘连动物模型,低雌激素状态对粘连形成的等级以及纤维化程度有显著影响。

Objective To establish a stable and reliable model of intrauterine adhesions in SD rats by simulating multiple factors of human etiology, and to lay a foundation for further study of pathogenesis and clinical intervention. Methods Total 48 female SD rats were randomly divided into 4 groups,Group A: uterine cavity injury + infection;Group B: uterine cavity injury + bilateral ovariectomy low estrogen state;Group C: uterine cavity injury + infection + low estrogen state;Group D: control group, without uterine cavity treatment, with 16 rats in each group, were sacrificed in batches on the 7th, 14th, 21st and 28th day after modeling, and the uterus were removed. Score criteria were used to evaluate the extent and extent of uterine adhesion according to the American Fertility Society(AFS). HE and Mason staining were used to observe the pathological changes of endometrium. The number of endometrial glands and the ratio of interstitial fibrosis area were counted on the 28th day after modeling. Results The differences in AFS score and modeling rate between the four groups were statistically significant(P all <0.05),and the AFS score and modeling rate between group B and C were higher than those in group A and D(P all <0.05). Compared with group D, the amount of endometrial glands in A,B,C groups were decreased and the area of endometrial fibrosis increased(P all <0.05). The amount of endometrial glands in group B and C with low estrogen was lower than those in group A,and the area of endometrial fibrosiseffected in group B and C with low estrogen was higher than those in group A(P all <0.05). Conclusion A Stable rat model of intrauterine adhesions can be established by multiple factors of injury,infection and low estrogen status. Low estrogen status has a significant effect on the grade of adhesions and fibrosis.