GnRH类似物对化疗大鼠卵泡凋亡的影响  

Effects of gonadotroph-releasing hormone analogues on follicle apoptosis in rats with chemotherapy-induced ovarian damage

作　　者：彭萍[1,2] 莫亚勤[1] 杨传红[2] 张伟[2] 张艳玲[2] 刘佳[2] 叶长烂[2] 杨冬梓[1] 

机构地区：[1]中山大学孙逸仙纪念医院妇产科,广东广州510120 [2]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》2010年第1期106-110,共5页Journal of Southern Medical University

基　　金：广东省科技计划项目(2007B080701014);广东省医学科学技术研究基金(A475);广东省科技计划项目(2008B080701026);广东省自然科学基金博士启动项目(8451001002001274);中山大学"临床医学研究5010计划"项目(2007017)

摘　　要：目的探讨促性腺激素释放激素激动剂(GnRH-a)、拮抗剂(GnRH-ant)对环磷酰胺(CTX)诱导的大鼠卵泡凋亡的干预作用。方法36只雌性Sprague-Dawley大鼠随机分为6组,即实验对照组、CTX组、GnRH-a+生理盐水(NS)组、GnRH-a+CTX组、GnRH-ant+NS组及GnRH-ant+CTX组,每组6只,于结束用药的第1～2周内的动情间期处死,采用末端转移酶介导的缺口末端标记法(TUNEL)结合透射电镜检测卵泡的凋亡情况。结果(1)TUNEL检测晚期生长卵泡的颗粒细胞凋亡率高于早期卵泡,使用CTX组别的卵母细胞、颗粒细胞的凋亡率高于相应对照组,其差异均有显著性意义(P<0.05)。其中GnRH-a两组[(33.40±4.59)～(73.25±5.35)]的颗粒细胞凋亡率较GnRH-ant两组[(27.46±4.52)～(49.38±5.02)]明显升高,其差异有显著性意义(P<0.05);但早期卵泡卵母细胞的凋亡率在GnRH-a两组[(23.48±4.25)～(36.15±4.23)]与GnRH-ant两组[(21.47±3.81)～(34.04±5.54)]的相应组间差异无显著性意义(P>0.05)。(2)电镜下在早期卵泡的卵母细胞、颗粒细胞、晚期生长卵泡的颗粒细胞可见凋亡的特征性改变。其中颗粒细胞核表现典型,可见典型的半月形凋亡小体形成,而卵母细胞核仅见染色质浓缩、边集、凝聚。结论GnRH-a、GnRH-ant对化疗大鼠的卵泡凋亡产生不同的调控作用,前者促进卵泡凋亡,而后者抑制卵泡凋亡。GnRH类似物主要调控卵泡颗粒细胞的凋亡,而对卵母细胞的凋亡调控作用不明显。Objective To study the effects of gonadotroph-releasing hormone （GnRH） agonist （GnRH-a） and GnRH antagonist （GnRH-ant） on cyclophosphamide （CTX）-induced follicle apoptosis in female rats. Methods Thirty-six female Sprague- Dawley rats were randomized into 6 groups, namely normal saline （NS）, CTX, GnRH-a＋NS, GnRH-a＋CTX, GnRH-ant＋NS, and GnRH-ant＋CTX groups. The rats were sacrificed between the first and second week after the treatments., and the follicle apoptosis was investigated using TUNEL assay and transmission electron microscopy. Results The apoptosis rate of the granulose cells in the follicles in late development was significantly higher than that in early follicles, and the apoptosis rate of the oocytes and granulose cells in rats with CTX treatment was significantly higher than that in rats without CTX treatment （P0.05）. The apoptosis rate of the granulose cells in GnRH-a groups （ranging from 33.40 ±4.59 to 73.25±5.35） was significantly higher than that in GnRH-ant groups （27.46±4.52 to 49.38±5.02, P0.05）, but there was no significant difference in the oocytes of early follicles between GnRH-a groups （23.48±4.25 to 36.15±4.23） and GnRH-ant groups （21.47±3.81 to 34.04±5.54, P0.05）. Electron microscopy revealed characteristic apoptotic changes of the oocytes in early follicles and granulose cells in early and late follicles. The apoptotic changes were especially typical in the granulose cells showing the formation of the apoptotic bodies, and the oocytes only showed chromatin condensation and aggregation. Conclusions In the rat mode, GnRH-a promotes while GnRH-ant suppressed follicle apoptosis induced by CTX. GnRH analogues regulates mainly granulose cell apoptosis, but have little effect on oocyte apoptosis.

关 键 词：促性腺激素释放激素类似物 卵泡 细胞凋亡 

分 类 号：R711.75[医药卫生—妇产科学]