1-磷酸-神经鞘氨醇干预化疗对荷瘤小鼠卵巢功能和抑瘤效果的影响  

Effect of sphingosine-1-phosphate on chemotherapy-induced ovarian damage and on the efficacy of chemotherapy in mice bearing S180 tumor

作　　者：彭萍[1] 吴璇[1] 关婷[1] 陈为[1] 张艳玲[1] 张伟[1] 杨传红[1] 叶长烂[1] 王善林[1] 

机构地区：[1]广州军区广州总医院妇产科,广东广州510010

出　　处：《南方医科大学学报》2012年第3期383-386,共4页Journal of Southern Medical University

基　　金：广东省科技计划项目(2010B031600265);广东省自然科学基金博士启动项目(8451001002001274);广东省医学科研基金(A2011446)

摘　　要：目的探讨凋亡抑制因子1-磷酸-神经鞘氨醇(S1P)对环磷酰胺(CTX)联合顺铂(DDP)诱导的S180荷瘤小鼠卵巢功能损害的干预作用及其对肿瘤化疗效果的影响。方法将52只C57BL/6雌性小鼠随机选取10只作为空白对照组,余皮下接种S180肿瘤细胞后随机分为3组,即荷瘤对照组、单纯化疗组、S1P+化疗组,每组14只。用药期间动态观察动情周期及肿瘤体积变化,于用药前、用药第11天左右的动情间期分批处死小鼠,分别称取体质量、卵巢质量及肿瘤质量;采用酶联免疫吸附(ELISA)法动态检测用药前后各组小鼠血清的卵泡刺激素(FSH)、黄体生成素(LH)及雌二醇(E2)水平的变化;卵巢组织连续病理切片,计算原始卵泡、生长卵泡数量的变化。每组剩余小鼠与成年雄性小鼠合笼,观察生育情况。结果(1)血清基础性激素水平:给药前,各组血清FSH、LH、E2水平无显著性差异(P>0.05);用药第11天左右,单纯化疗组血清FSH水平明显高于其余3组、E2水平明显低于其余3组,其差异均有显著性意义(P<0.01),但血清LH水平各组间无显著性差异(P>0.05);S1P+化疗组血清FSH、LH、E2水平与两对照组均无显著性差异(P>0.05);(2)卵泡数量及卵巢质量:用药第11天左右,单纯化疗组原始卵泡数和卵巢质量明显低于其余3组(P<0.01),其生长卵泡数亦明显低于空白对照组、荷瘤对照组(P<0.01),但与S1P+化疗组的差别无显著性意义(P>0.05)。S1P+化疗组原始卵泡数、生长卵泡数及卵巢质量与空白对照组、荷瘤对照组比较差异均无统计学意义(P>0.05);(3)肿瘤质量和抑瘤率:给药第11天左右,与荷瘤对照组比较,单纯化疗组、S1P+化疗组的皮下肿瘤体积增长速度均受到明显抑制,两组的肿瘤质量与荷瘤对照组相比均有显著性差异(P<0.01),且两组的抑瘤率均高于60%。结论 S1P可以在不影响肿瘤化疗效果的同时,预防化疗对小鼠卵巢功能的损害。Objective To investigate the effects of sphingosine-1-phosphate（S1P） on cyclophosphamid（CTX） and cisplatin（DDP）-induced ovarian damage and on the efficacy of chemotherapy in mice bearing S180 murine sarcoma.Methods Fifty-two female C57BL/6 mice were randomized into normal control group（n=10）,tumor-bearing model group（n=14）,CTX＋DDP group（n=14）,and S1P＋CTX＋DDP group（n=14）.Before medication and on day 11 of medication during diestrus stage,the mice were sacrificed to measure the ovarian weight,numbers of primordial follicles and growing follicles,tumor weight,and serum levels of follicle-stimulating hormone（FSH）,luteinizing hormone（LH） and estradiol（E2）.Results At day 11 of medication,the levels of serum FSH and E2,but not LH,showed significant differences in CTX＋DDP group from those in the other groups（P0.01）.FSH,E2,and LH levels were comparable between S1P＋CTX＋DDP group and the control group（P0.05）.The number of primodial follicles and weight of ovaries in CTX＋DDP group decreased significantly compared to those in the other groups（P0.01）.The number of growing follicles in CTX＋DDP group was significantly lower than that in the control and model groups（P0.01）,but similar to that in S1P group（P0.05）.The number of primodial follicles and growing follicles and ovarian weight in S1P＋CTX＋DDP group were close to those in the control and model groups（P0.05）.In CTX＋DDP and S1P＋CTX＋DDP groups,the tumor weight were significantly lower than that in the other two groups（P0.01）,and the tumor inhibition rates were both higher than 60%.Conclusion S1P can ameliorate chemotherapy-induced ovarian damage in mice without affecting the efficacy of chemotherapy.

关 键 词：1-磷酸-神经鞘氨醇 环磷酰胺 顺铂 卵巢 抑瘤作用 S180细胞 C57BL/6小鼠 

分 类 号：R73-36[医药卫生—肿瘤]