雄激素致无排卵大鼠卵巢nNOS、eNOS、ET-1的表达

Expression of nNOS,eNOS,ET-1 in Ovary in Androgen-induced Sterile Rats

目的观察雄激素致无排卵大鼠(ASR)血浆及卵巢血管舒张因子一氧化氮(NO)、一氧化氮合酶(nNOS、eNOS)、环磷酸鸟苷(cGMP)、血管收缩因子内皮素1(ET-1)、血管紧张素Ⅱ(ATⅡ)的变化,探讨卵巢血管舒-缩因子在无排卵发病机制中的作用。方法建立雄激素致无排卵大鼠模型,分为模型组和正常组。采用放射免疫法测定模型组、正常组大鼠血浆NO、cGMP、ET-1、ATⅡ以及血清雌二醇(E2)、孕酮(P)、睾酮(T)含量;采用免疫组化法检测大鼠卵巢nNOS、eNOS、ET-1表达;采用HE染色观察大鼠卵巢组织形态学变化。结果与正常组比较,模型组大鼠血浆NO、cGMP含量降低(P<0.01),血浆ET-1、ATⅡ含量升高(P<0.01)。血清E2、T含量及E2/P显著升高(P<0.01),血清P含量无统计学差异(P>0.05);与正常组比较,模型组大鼠卵巢颗粒细胞以及髓质nNOS、eNOS表达减弱(P<0.01),ET-1表达增强(P<0.01);正常组大鼠卵巢皮质可见发育期各级卵泡及黄体;模型组大鼠卵巢皮质卵泡囊状扩张,颗粒细胞层极薄。结论雄激素致无排卵大鼠血浆及卵巢血管舒张因子降低、收缩因子增高,可能使卵巢血液供应障碍、颗粒细胞凋亡,导致卵泡在排卵前闭锁,无排卵的发生。

Objective To observe the changes of plasma and ovarian nitric oxide（NO）,nitric oxide synthase（nNOS,eNOS）and cyclic guanosine monophosphate（cGMP）of the vasorelaxation factors,endothelin-1（ET-1）and angiotensin Ⅱ（AT Ⅱ）of the vasoconstriction factors in androgen-induced sterile rats（ASR）,and explore the action of vasorelaxation factors and vasoconstriction factors on the anovular diseases.Methods ASR model was established by injecting androgen.Rats were divided into ASR model group and normal group.The level of plasma NO,cGMP,ET-1 and ATⅡ,serum estradio（lE2）,progesterone（P）and testosterone（T）was detected by radioimmunoassay.The expression of nNOS,eNOS and ET-1 in the ovary was detected by immunohistochemical method.The morphological structures of the ovary were observed by HE dyeing.Results As compared with nomal group,the level of plasma No and cGMP was lower（P 〈0.01）,the level of plasma ET-1 and ATⅡwas higher in model group（P〈 0.01）.The level of serum E2,T and E2/P was higher（P〈 0.01）,the level of serum P has no obviously statistics difference in model group（P 〉0.05）;As compared with the normal group,the expression of nNOS,eNOS in granular cells and ovarian medulla was lower（P 〈0.01）,the expression of ET-1 in granular cell and ovarian medulla was higher in the model rats（P〈 0.01）;There were abundant follicles during all growth period and corpus luteums in ovary in the normal rats,the follicles were ectatic and granular layer was very thin in model rats.Conclusion Plasma and ovarian vasorelaxation factors were lower and vasoconstriction factors were higher in ASR,which might decrease the blood supply in the region of ovary,promote apoptosis of granular cell,lead to follicular atresia and anovulation.