负载SDF-1α的温度敏感性水凝胶预防宫腔粘连及促进子宫内膜再生修复的效果

Effect of thermosensitive hydrogel containing stromal cell-derived factor-1α on intrauterine adhesion and endometrium regeneration in rabbits

目的考察负载重组人基质细胞衍生因子-1α(recombinant human stromal cell-derived factor-1 alpha,rh SDF-1α)的温度敏感性水凝胶PLA/PEG三嵌段聚合物(PLA-PEG-PLA,PLEL)对预防宫腔粘连、促进子宫内膜再生修复的效果。方法 24只成年新西兰雌兔(48条子宫)分为4组(n=12):1自然修复组,纵行剪开子宫全长,剪去子宫内膜,止血后缝合子宫切口;2PLEL治疗组,缝合子宫切口后向宫腔内注射PLEL水凝胶;3PLEL-rh SDF-1α治疗组,缝合子宫切口后向宫腔内注射复合rh SDF-1α的PLEL水凝胶;4假手术组,仅行开腹手术,不处理子宫。分别于术后7 d和28 d取子宫标本,免疫荧光染色观察间质干细胞(mesenchymal stem cells,MSCs)表面标志CD44和CD90的表达,组织学染色观察子宫内膜修复情况。结果自然修复组宫腔粘连,无内膜上皮组织再生。与PLEL治疗组比较,PLEL-rh SDF-1α治疗组有大量MSCs归巢至再生内膜组织(P<0.05),再生内膜上皮层周长/基底层周长比值更大(P<0.05),但均不及假手术组(P<0.05)。结论温度敏感性PLEL水凝胶复合rh SDF-1α具有预防子宫宫腔粘连、促进子宫内膜再生修复的作用。

Objective To evaluate the effect of thermosensitive poly（ lactic acid）-polyethylene glycol- poly（ lactic acid） block polymer（ PLEL） hydrogel containing recombinant human stromal cell-derived factor-1α（ rh SDF-1α） on preventing intrauterine adhesion and promoting the regeneration of endometrium.Methods Twenty-four adult female New Zealand rabbits（ 48 uteruses） were randomly divided to 4 groups：spontaneous regeneration group（ n = 12） which was treated by cutting the uterus lengthwise,removing the endometrium with scissors,and then suturing the incision after hemostasis,PLEL treatment group（ n = 12）which was treated by injecting PLEL hydrogel after suturing the incision,PLEL-rh SDF-1α treatment group（ n = 12） which was treated by injecting PLEL hydrogel containing rh SDF-1α after suturing the incision,and sham operation group（ n = 12） which just exposed the uterus via an abdominal midline incision. All the rabbits underwent euthanasia on postoperative 7 and 28 d to get the uterus samples. The expression levels of CD44 and CD90 were determined by immunofluorescence staining,and the regenerative endometrium was observed by immunohistochemical staining. Results Epithelial tissue was not regenerated nearly in the spontaneous regeneration group. There were more MSCs homing to the regenerative endometrium in the PLELrh SDF-1α treatment group than in the PLEL treatment group（ P〈 0. 05）,and the ratio of epithelial layer length to basal layer length was larger（ P 〈0. 05）. But the sham operation group was better than all of them（ P〈 0. 05）. Conclusion Thermosensitive PLEL hydrogel containing rh SDF-1α is effective on preventing intrauterine adhesion and promoting the regeneration of endometrium.