人脐带间充质干细胞对输卵管炎大鼠输卵管超微结构和功能的改变

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目的:探讨人脐带Wharton’s间充质干细胞(Wharton’s jelly-derived mesenchymal stem cells,WJMSCs)在输卵管炎性不孕症治疗中的应用前景。方法:成年雌性Wistar大鼠50只,随机分为输卵管炎症模型组(n=40)和对照组(n=10)。其中,模型组大鼠双侧输卵管注入混合菌后再随机分成5组,急性治疗前组(n=5),于造模后第20日取材;急性治疗组(n=10),于造模第20日,给予腹腔注射WJMSCs(1×106/ml),7 d/次,共3次,疗程结束1周后5只取材;慢性治疗前组(n=5),于造模后30 d取材;慢性治疗组(n=10),于造模第30日开始给予WJMSCs;方法同急性治疗组,疗程结束1周后5只取材;慢性模型组(n=10),造模后不给予任何处理,第51日5只取材,所有余下雌鼠分别与雄鼠同笼。检测比较急、慢性输卵管炎模型大鼠腹腔注射WJMSCs治疗前、后血清INF-γ和TNF-α水平、输卵管超微结构、单位面积输卵管腔上皮皱褶长度(Lu)和分泌颗粒的密度(D),以及各组受孕率及产仔数。结果:急性输卵管炎期,输卵管上皮被破坏,间质水肿,治疗后基本恢复正常。慢性输卵管炎期,上皮扁平化,黏膜下纤维化,治疗后无明显改善。急性输卵管炎治疗前组Lu值无明显变化,而D值显著下降,治疗后恢复正常;慢性输卵管炎治疗前组Lu、D值均明显降低,治疗后无明显好转。急、慢性输卵管炎治疗前组血清TNF-α和INF-γ水平均明显增高,治疗后急性组恢复到正常水平,而慢性治疗组虽有下降,但仍高于正常水平。急性输卵管炎治疗组受孕率、产仔数恢复正常。慢性输卵管炎治疗前、后,其受孕率、产仔数均明显下降。结论:WJMSCs腹腔注射治疗大鼠急性输卵管炎,能降低血清炎症因子,恢复输卵管结构和功能,恢复生育功能,但对慢性输卵管炎的治疗效果不明显,提示在急性期治疗输卵管炎有可能防止继发不孕的发生。 Objective: To explore the potential application of Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) in the treatment of tubal infertility. Methods: Fifty adult female Wistar rats were randomly divided into the fallopian tube inflammation model group (n = 40) and the control group (n = 10). The rats in the untreated group were randomly divided into five groups after injection of the mixed fallopian tubes. The rats in the acute treatment group (n = 5) were drawn on the 20th day after the model was established. The acute treatment group (n = 10) On the 20th day, WJMSCs (1 × 106 / ml) were injected intraperitoneally for 7 days for 3 times. One week after the end of the course of treatment, 5 were taken. In the group of chronic pretreatment (n = 5) The rats in the chronic treatment group (n = 10) were given WJMSCs on the 30th day after the model was established. The methods were the same as those in the acute treatment group. Five weeks after the end of the treatment, 5 were taken. The chronic model group (n = 10) Any treatment, the first 51 days of 5 drawn, all the remaining female rats were the same cage with male. To detect the levels of INF-γ and TNF-α, the tubal ultrastructure, the luminal lumen folds per unit area (Lu) and the density of secretory granules (D) before and after WJMSCs treatment in acute and chronic salpingitis models. ), As well as the pregnancy rate and litter size of each group. Results: Acute salpingitis, tubal epithelium was destroyed, interstitial edema, basically returned to normal after treatment. Chronic salpingitis, epithelial flat, submucosal fibrosis, no significant improvement after treatment. There was no significant change in Lu value before acute salpingitis treatment, but the value of D decreased significantly and returned to normal after treatment. The Lu and D values ​​of the treatment group before chronic salpingitis were significantly decreased, but no significant improvement was observed after treatment. Serum levels of TNF-α and INF-γ in patients with acute or chronic salpingitis were significantly higher than those before treatment, and the acute group returned to normal after treatment, while the chronic treatment group was decreased, but still higher than the normal level. Acute salpingitis treatment group pregnancy rate, litter size returned to normal. Chronic salpingitis before and after treatment, the pregnancy rate, litter size were significantly decreased. Conclusion: WJMSCs intraperitoneal injection of acute salpingitis in rats, can reduce serum inflammatory cytokines, restore tubal structure and function, restore fertility, but the treatment of chronic salpingitis is not obvious, suggesting that the treatment of salpingitis in the acute phase may prevent the successor Infertility occurs.
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