人脐带间充质干细胞联合透明质酸钠凝胶局部注射治疗大鼠宫腔粘连的效果及机制  

Effect of local injection of human umbilical cord mesenchymal stem cells combined with sodium hyaluronate gel in the treatment of intrauterine adhesions in rats and its mechanism

作　　者：王志景 何全中 WANG Zhijing;HE Quanzhong(Department of Obstetrics and Gynecology,the Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003,Henan Province,China)

机构地区：[1]新乡医学院第三附属医院妇产科,河南新乡453003

出　　处：《新乡医学院学报》2024年第9期809-815,共7页Journal of Xinxiang Medical University

摘　　要：目的探讨人脐带间充质干细胞(hUC-MSCs)联合透明质酸钠凝胶局部注射治疗宫腔粘连大鼠的效果及可能机制。方法按照随机数字表法将25只无特定病原级雌性Sprague Dawley大鼠分为空白对照组、宫腔粘连组、透明质酸钠凝胶组、hUC-MSCs组、hUC-MSCs+透明质酸钠凝胶组,每组5只。空白组大鼠不做任何处理;其余4组大鼠使用体积分数950 mL·L^(-1)乙醇注射法制备宫腔粘连模型。宫腔粘连模型制备1周后,hUC-MSCs组、hUC-MSCs+透明质酸钠组大鼠双侧子宫角内分别注射100μL的1×10^(10) L^(-1) hUC-MSCs混悬液,宫腔粘连组、透明质酸钠组大鼠双侧子宫角内注射生理盐水100μL;随后,透明质酸钠组和hUC-MSCs+透明质酸钠组大鼠双侧子宫角内注射透明质酸钠凝胶300μL,宫腔粘连组和hUC-MSCs组大鼠双侧子宫角内注射等量生理盐水。干预3 d后,将5组大鼠与具有生殖能力的成熟雄大鼠依照1∶2的数量混合饲养、进行交配;交配7 d观察大鼠阴道栓,以确定交配成功。抽取5组妊娠大鼠腹主动脉血,采用酶联免疫吸附试验法检测大鼠血清中白细胞介素-6(IL-6)、白细胞介素-8(IL-8)水平;取血后,将大鼠过量麻醉处死,开腹取双侧子宫,用生理盐水冲洗,首先计数妊娠孕囊数量;然后,小心分离子宫内膜组织,采用Western blot法检测大鼠子宫内膜组织中基质金属蛋白酶-9(MMP-9)、转化生长因子β1(TGF-β1)表达水平。结果宫腔粘连组、透明质酸钠组、hUC-MSCs组、hUC-MSCs+透明质酸钠组大鼠妊娠孕囊数量显著少于空白对照组,透明质酸钠组、hUC-MSCs组、hUC-MSCs+透明质酸钠组大鼠妊娠孕囊数量显著多于宫腔粘连组,hUC-MSCs+透明质酸钠组大鼠妊娠孕囊数量显著多于透明质酸钠组和hUC-MSCs组(P<0.05);透明质酸钠组与hUC-MSCs组大鼠妊娠孕囊数量比较差异无统计学意义(P>0.05)。宫腔粘连组、透明质酸钠组、hUC-MSCs组、hUC-MSCs+透明质酸钠组大鼠血Objective To investigate the effect of local injection of human umbilical cord mesenchymal stem cells(hUC-MSCs)combined with sodium hyaluronate gel in the treatment of intrauterine adhesion in rats and its possible mechanisms.Methods Twenty-five specific pathogen-free female Sprague Dawley rats were divided into a blank control group,an intrauterine adhesion group,a sodium hyaluronate group,an hUC-MSCs group,and an hUC-MSCs+sodium hyaluronate group according to the random number table method,with 5 rats in each group.The rats in the blank control group received no treatment,while the rats in the rest four groups were injected with 950 mL·L^(-1) ethanol to prepare intrauterine adhesion models.One week following the establishment of the intrauterine adhesion models,100μL of 1×10^(10) L^(-1) hUC-MSCs suspension was injected into the bilateral uterine horns of rats in the hUC-MSCs group and hUC-MSCs+sodium hyaluronate group;and 100μL of normal saline was injected into the bilateral uterine horns of rats in the intrauterine adhesion group and sodium hyaluronate group.Subsequently,300μL of sodium hyaluronate gel was injected into the bilateral uterine horns of rats in the sodium hyaluronate group and hUC-MSCs+sodium hyaluronate group;while,the same amount of normal saline was injected into the bilateral uterine horns of rats in the intrauterine adhesion group and hUC-MSCs group.After three days of intervention,all female rats in the five groups were combined with mature male rats possessing reproductive ability at a ratio of 1:2 and then mated.The vaginal plugs of the female rats were observed for seven days to confirm successful mating.The abdominal aortic blood from pregnant rats in the five groups was extracted,and the serum levels of interleukin-6(IL-6)and interleukin-8(IL-8)were determined by using enzyme-linked immunosorbent assay.After blood collection,the rats were euthanized with excessive anesthesia,and subsequently,the uterus was removed and rinsed with normal saline.Firstly,the quantity of gestational

关 键 词：宫腔粘连 人脐带间充质干细胞 透明质酸 纤维化 炎症反应 

分 类 号：R711.32[医药卫生—妇产科学]