Menstrual blood derived mesenchymal stem cells combined with Bushen Tiaochong recipe improved chemotherapy-induced premature ovarian failure in mice by inhibiting GADD45b expression in the cell cycle pathway

经血间充质干细胞联合补肾调冲方抑制细胞周期通路GADD45b表达改善小鼠化疗所致卵巢早衰

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作者:Fengyi Guo, Tian Xia, Yedan Zhang, Xiaotong Ma, Zhongrui Yan, Shaohua Hao, Yali Han, Ruihong Ma, Yuan Zhou, Xue Du

Background

To investigate the therapeutic effects of menstrual blood derived mesenchymal stem cells (MB-MSCs) combined with Bushen Tiaochong recipe (BSTCR) on epirubicin induced premature ovarian failure (POF) in mice.

Conclusions

MB-MSCs combined with BSTCR improved the ovarian function of epirubicin induced POF mice, which might be related to the inhibition of GADD45b expression and the promotion of CyclinB1 and CDC2 expressions. The combined treatment had better therapeutic efficacy than BSTCR or MB-MSCs alone.

Methods

Twenty-four female C57BL/6 mice of 6-8 weeks were intraperitoneally injected with epirubicin to induce POF, and then they were randomized into 4 groups of 6 mice each and treated with PBS, MB-MSCs, BSTCR, and MB-MSCs combined with BSTCR, respectively. Six mice of the same age were used as controls. Vaginal smear, TUNEL and hematoxylin-eosin staining were to observe estrous cycles, ovarian cell apoptosis and follicles. Enzyme-linked immunosorbent analysis determined serum estradiol, follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) levels. RT-qPCR and Western Blot analysis were to determine GADD45b, CyclinB1, CDC2 and pCDC2 expressions.

Results

Epirubicin treatment resulted in a decrease in the number of primordial, primary, secondary and antral follicles, an increase in the number of atretic follicles and ovarian cell apoptosis, a decrease in estradiol and AMH levels, an increase in FSH levels, and estrous cycle arrest. However, MB-MSCs combined with BSTCR rescued epirubicin induced POF through down-regulating GADD45b and pCDC2 expressions, and up-regulating CyclinB1 and CDC2 expressions. The combined treatment showed better therapeutic efficacy than BSTCR or MB-MSCs alone. Conclusions: MB-MSCs combined with BSTCR improved the ovarian function of epirubicin induced POF mice, which might be related to the inhibition of GADD45b expression and the promotion of CyclinB1 and CDC2 expressions. The combined treatment had better therapeutic efficacy than BSTCR or MB-MSCs alone.

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