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热休克预处理大鼠骨髓间充质干细胞预防顺铂诱导的卵巢颗粒细胞凋亡
谢嘉欣,李欣然,王清,汪庆如,付霞霏*
0
(南方医科大学珠江医院妇产科, 广州 510280
*通信作者)
摘要:
目的 探讨热休克预处理大鼠骨髓间充质干细胞(MSC)预防顺铂诱导的卵巢颗粒细胞(GC)凋亡的效果。方法 分离培养大鼠骨髓MSC,设置不同热休克预处理时间,采用流式细胞术检测细胞凋亡情况,确定最佳热休克预处理条件。以顺铂模拟化学治疗的卵巢局部微环境,将MSC分为对照组、热休克预处理组、顺铂组及热休克预处理+顺铂组,检测各组MSC凋亡情况。分离、培养大鼠GC,采用顺铂诱导卵巢GC损伤的体外模型,将GC分为对照组、顺铂组、MSC预防+顺铂组、热休克预处理MSC(HS-MSC)预防+顺铂组,检测各组GC的凋亡情况。结果 热休克预处理能够减轻MSC凋亡,最佳热休克预处理条件为42℃热休克处理1 h。在顺铂模拟化学治疗的卵巢局部微环境中,热休克预处理+顺铂组MSC凋亡率为(11.94±0.63)%,低于顺铂组的(14.30±0.80)%,差异有统计学意义(P<0.05)。在顺铂诱导卵巢GC损伤的体外模型中,顺铂组GC的凋亡率为(53.81±1.89)%,HS-MSC预防+顺铂组GC的凋亡率为(39.88±1.65)%,两组比较差异有统计学意义(P<0.05)。结论 热休克预处理能够提高化学治疗环境下MSC的抗凋亡能力。热休克预处理的MSC能够抑制顺铂诱导的卵巢GC凋亡,有预防性保护作用。
关键词:  热休克  间质干细胞  卵巢功能不全  化学治疗
DOI:10.16781/j.0258-879x.2020.01.0057
投稿时间:2019-09-07修订日期:2019-11-06
基金项目:广东省自然科学基金(2018A030313167).
Heat shock-pretreated rat bone marrow-derived mesenchymal stem cells prevent apoptosis of ovarian granulosa cells induced by cisplatin
XIE Jia-xin,LI Xin-ran,WANG Qing,WANG Qing-ru,FU Xia-fei*
(Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong, China
*Corresponding author)
Abstract:
Objective To study the preventive effects of heat shock-pretreated rat bone marrow-derived mesenchymal stem cells (MSCs) on the apoptosis of ovarian granulosa cells (GCs) induced by cisplatin. Methods Rat bone marrow-derived MSCs were isolated, cultured and identified. After heat shock pretreatment for different durations, the apoptotic rates of MSCs were detected to determine the optimal condition of heat shock pretreatment. Cisplatin was added to simulate chemotherapy microenvironment in the ovary. MSCs were divided into normal group (without treatment), heat shock pretreatment group, cisplatin group (without heat shock pretreatment), and heat shock pretreatment+cisplatin group. The apoptotic rate of MSCs was determined. The ovarian GCs were isolated and divided into normal group (without treatment), cisplatin group, MSC prevention group (co-cultured with MSCs before adding cisplatin), and heat shock pretreatment MSC (HS-MSC) prevention group (co-cultured with HS-MSCs before adding cisplatin). The apoptotic rate of GCs was detected. Results Heat shock pretreatment could reduce the apoptosis of MSCs. After receiving heat shock pretreatment at 42℃ for 1 h, MSCs presented the lowest apoptotic rate. After adding cisplatin, the apoptotic rate of MSCs in heat shock pretreatment+ cisplatin group was significantly lower than that of cisplatin group ([11.94±0.63]% vs[14.30±0.80]%, P<0.05). The apoptotic rate of GCs in HS-MSC prevention+cisplatin group was significantly lower than that of cisplatin group ([39.88±1.65]% vs ([53.81±1.89]%, P<0.05). Conclusion Heat shock pretreatment can alleviate the apoptosis of MSCs during chemotherapy. Heat shock-pretreated MSCs have preventive effects on cisplatin-induced GC apoptosis.
Key words:  heat shock  mesenchymal stem cells  ovarian insufficiency  chemotherapy