GnRH类似物对化疗大鼠卵巢局部Bcl-2基因家族表达的影响  

Effect of GnRH analogs on the expression of Bcl-2 gene family in the ovary of rats with cyclophosphamide-induced ovarian damage

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

机构地区：[1]广州军区广州总医院妇产科,广东广州510010 [2]中山大学第二附属医院妇产科,广东广州510120

出　　处：《南方医科大学学报》2008年第11期2014-2017,共4页Journal of Southern Medical University

基　　金：广东省医学科学技术研究基金(A475);广东省科技计划项目(2007B080701014);教育部高等学校博士学科点专项科研基金项目(20050558093)

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)干预环磷酰胺(CTX)诱导的大鼠卵巢功能损害的可能作用机制。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,观察卵泡数量、卵巢重量的变化,并采用半定量RT-PCR检测卵巢组织Bcl-2及Bax的mRNA变化。结果(1)GnRH-a两组的原始卵泡数较其他各组多,生长卵泡数较其他各组少;与其他各组比较,GnRH-ant+CTX组和CTX组的原始卵泡数最少,生长卵泡数最多,其差异均有显著性意义(P<0.05)。(2)GnRH-a两组的卵巢重量最低,与其余组的差异均有显著性意义(P<0.05)。(3)Bcl-2mRNA的表达仅GnRH-ant+NS组与其余组间差异有显著性意义(P<0.05)。而Bax-mRNA的表达变化明显,其中GnRH-a两组的表达明显高于对照组(P<0.05),近似CTX组(P>0.05);而GnRH-ant+NS组明显低于对照组(P<0.05),GnRH-ant+CTX组近似对照组(P>0.05)。结论在大鼠动物模型上,GnRH类似物干预CTX诱导的大鼠卵巢功能损害的可能作用机制之一是通过调控卵巢局部的BaxmRNA表达而实现;其中GnRH-a促进细胞凋亡、抑制细胞增殖可能使卵泡对CTX相对不敏感,而GnRH-ant抑制细胞凋亡、促进细胞增殖则可能使卵泡对CTX相对敏感。Objective To study the effect of gonadotroph-releasing hormone （GnRH） agonist （GnRH-a） and GnRH antagonist （GnRH-ant） against cyclophosphamide （CTX）-induced gonadotoxicity in female rats. Methods Thirty-six female SD rats were divided randomly into 6 groups to receive treatment with normal saline （NS）, CTX, GnRH-a＋NS, GnRH-a＋CTX, GnRH-ant＋NS, GnRH-ant＋CTX, respectively. The rats were sacrificed between the first and second week after termination of the medication to compare the weight of the ovaries, the number of the primordial follicles and the follicle growth. The expressions of bcl-2 and bax mRNA in the ovaries were examined using RT-PCR. Results The number of the primordial follicles was significantly greater and that of the growing follicles significantly lower in GnRH-a＋NS and GnRH-a＋CTX groups than in the GnRH-ant＋CTX and CTX groups （/9〈0.05）. The rats in GnRH-a＋NS and GnRH-a＋CTX groups had the lowest ovarian weight among 6 the groups （P〈0.05）. The bcl-2 mRNA level in the GnRH-ant＋NS group was significantly higher than that in the other groups （P〈0.05）. The Bax mRNA in the GnRH-a＋NS and GnRH-a＋CTX groups was significantly higher than that in the NS group （P〈0.05）, but close to that in the CTX group （P〉0.05）; bax mRNA expression in the GnRH-ant＋NS group was significantly lower than that in the NS group （P〈0.05）, but in GnRH-ant＋CTX group, its expression was close to that in the NS group （P〉0.05）. Conclusions In female rats exposed to CTX, the GnRH analogs provides ovarian protection against CTX-induced gonadotoxicity by regulating the expression of the Bax mRNA in the ovary. GnRH-a may decrease the sensitivityof the follicles to CTX-induced gonadotoxicity by promoting follicle apoptosis and inhibiting follicle proliferation, and GnRH-ant increases the sensitivity to the CTX through a reverse effect on the follicles.

关 键 词：促性腺激素释放激素类似物 卵巢功能 细胞凋亡 BCL-2 Bax 

分 类 号：R714.8[医药卫生—妇产科学] R711.7[医药卫生—临床医学]