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在大鼠模型中,骨髓基质细胞联合粒细胞集落刺激因子用于治疗化疗诱导的卵巢功能衰竭

Bone Marrow Stromal Cells with the Granulocyte Colony-Stimulating Factor in the Management of Chemotherapy-Induced Ovarian Failure in a Rat Model.

作者信息

Sameni Hamid Reza, Seiri Maryam, Safari Manouchehr, Tabrizi Amjad Mohammad Hasan, Khanmohammadi Nasrin, Zarbakhsh Sam

机构信息

Nervous System Stem Cells Research Center, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.

出版信息

Iran J Med Sci. 2019 Mar;44(2):135-145.

Abstract

BACKGROUND

Bone marrow stromal cells (BMSCs), as a type of mesenchymal stem cells, and the granulocyte colony-stimulating factor (G-CSF), as a type of growth factor, may recover damaged ovaries. The aim of the present study was to investigate the effects of the coadministration of BMSCs and the G-CSF on damaged ovaries after creating a chemotherapy model with cyclophosphamide (CTX) in rats.

METHODS

The present study was performed in Semnan, Iran, in the late 2016 and the early 2017. BMSCs were cultured and were confirmed using the CD markers of stromal cells. Forty female Wistar rats were randomly divided into 4 groups. The rats were injected intraperitoneally with CTX for 14 days to induce chemotherapy and ovarian destruction. Then, the BMSCs were injected into bilateral ovaries and the G-CSF was injected intraperitoneally, individually and together. Four weeks later, the number of ovarian follicles using H&E staining, the number of apoptotic granulosa cells using the TUNEL assay, the number of produced oocytes from the ovaries, and the levels of serum E2 and FSH using an ELISA reader were assessed. Statistical analysis was done using one-way ANOVA with SPSS, version 16.0.

RESULTS

The results showed that the effects of the coadministration of 2×10 BMSCs and 70 µg/kg of the G-CSF were significantly more favorable than those in the control group (P<0.001), the BMSC group (P=0.016), and the G-CSF group (P<0.001) on the recovery of damaged ovaries.

CONCLUSION

The efficacy of the coadministration of BMSCs and the G-CSF in the recovery of ovaries damaged by chemotherapy was high by comparison with the administration of either of them separately.

摘要

背景

骨髓基质细胞(BMSCs)作为一种间充质干细胞,以及粒细胞集落刺激因子(G-CSF)作为一种生长因子,可能会使受损卵巢恢复。本研究的目的是探讨在大鼠中用环磷酰胺(CTX)建立化疗模型后,联合给予BMSCs和G-CSF对受损卵巢的影响。

方法

本研究于2016年末和2017年初在伊朗塞姆南进行。培养BMSCs并使用基质细胞的CD标志物进行确认。40只雌性Wistar大鼠随机分为4组。大鼠腹腔注射CTX 14天以诱导化疗和卵巢破坏。然后,将BMSCs分别或联合注射到双侧卵巢,并腹腔注射G-CSF。四周后,使用苏木精-伊红(H&E)染色评估卵巢卵泡数量,使用TUNEL法评估凋亡颗粒细胞数量,评估卵巢产生的卵母细胞数量,并使用酶标仪测定血清雌二醇(E2)和促卵泡生成素(FSH)水平。使用SPSS 16.0版进行单因素方差分析进行统计分析。

结果

结果表明,联合给予2×10个BMSCs和70μg/kg G-CSF对受损卵巢恢复的效果明显优于对照组(P<0.001)、BMSC组(P=0.016)和G-CSF组(P<0.001)。

结论

与单独给予BMSCs或G-CSF相比,联合给予BMSCs和G-CSF对化疗损伤卵巢的恢复效果显著。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3375/6423433/a4f445418744/IJMS-44-135-g001.jpg

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