谷氨酸钠诱导肥胖性不孕大鼠弓状核NPY及GnRH的表达

目的:探讨谷氨酸钠诱导肥胖性不孕大鼠弓状核神经肽Y(NPY)及促性腺激素释放激素(GnRH)的表达。方法:给新出生雌性Wistar大鼠皮下注射谷氨酸钠,连续5天,建立肥胖模型。观察NPY及GnRH在其下丘脑弓状核表达的变化;并测定血清雌二醇(E2)、睾酮(T)、瘦素(leptin)、卵泡刺激素(FSH)、黄体生成素(LH)的变化。结果:80%注射谷氨酸钠的大鼠呈能量失衡致肥胖状态;血清E2、T、leptin水平较对照组明显升高(P<0.05),FSH、LH水平较对照组明显降低(P<0.05);下丘脑弓状核NPY表达较对照组增强(P<0.05),GnRH表达较对照组减弱(P<0.05)。结论:谷氨酸钠诱导肥胖大鼠由于神经内分泌-代谢失调而引起GnRH水平降低,导致下丘脑-垂体-卵巢轴功能失调性无排卵而致不孕。     

损毁弓状核致大鼠肥胖型无排卵机制探讨

目的:探讨注射谷氨酸钠损毁弓状核致大鼠肥胖后对其不孕的影响.方法:给新出生雌性Wistar大鼠皮下注射谷氨酸钠(实验组),连续5天,以损毁其弓状核建立肥胖模型.对照组注射等量0.9%氯化钠液,连续5天.最终筛选出实验组肥胖不孕大鼠模型20只和对照组大鼠20只.观察两组神经肽Y(NPY)、瘦素受体(leptin R)及促性腺激素释放激素(GnRH)在其下丘脑弓状核的表达变化;并测定血清雌二醇(E2)、睾酮(T)、瘦素(leptin)、卵泡刺激素(FSH)、黄体生成素(LH)的水平.结果:在实验组大鼠中,血清E2、T、leptin水平较对照组明显升高(P<0.05),FSH、LH水平较对照组明显降低(P<0.05);下丘脑弓状核NPY表达较对照组增强(P<0.05),而leptin R及GnRH免疫阳性胞体及纤维表达较对照组减弱(P<0.05).结论:损毁弓状核致大鼠肥胖由于神经内分泌-代谢失调而引起GnRH水平降低,导致下丘脑-垂体-卵巢轴功能失调性无排卵而引起不孕.     

吗啡对雌性大鼠性腺轴和骨组织的影响

目的:研究吗啡对雌性大鼠性腺轴和骨组织的影响。方法:选取3月龄雌性大鼠45只,随机分为吗啡组30只和对照组15只。吗啡组采用剂量递增法皮下注射盐酸吗啡12周,对照组注射同等体积的生理盐水12周。放射免疫法测定血清FSH、LH、E2、P;免疫组织化学检测下丘脑、垂体、卵巢雌激素受体(ER)和β-内啡肽(β-EP)的表达;原位杂交方法测定下丘脑、垂体和卵巢的μ-阿片受体mRNA的表达;双能X线骨密度测量仪测量不同部位的骨密度值;测量骨代谢生化指标;对骨组织切片进行形态计量分析;并用RT-PCR方法检测骨组织中雌激素受体(ER)mRNA的变化。结果:(1)吗啡组FSH、LH、E2、P基础分泌较对照组降低(P<0·01,P<0·05,P<0·01,P<0·05);(2)吗啡组大鼠性腺轴各组织中ER平均光密度值均显著降低(P均<0·01);(3)吗啡组大鼠下丘脑、垂体β-内啡肽的含量下降,而μ-阿片受体mRNA表达增强;(4)吗啡组大鼠股骨远侧干骺端和胫骨近侧干骺端骨密度以及骨组织中ERmRNA表达均较对照组显著下降(P<0·05),组织切片观察显示,吗啡组大鼠骨小梁纤细、断裂、形态结构完整性差,骨髓腔大小不一,对照组大鼠骨小梁粗壮、饱满、形态结构完整,骨髓腔相对较小,计量分析显示,吗啡组骨小梁面积明显低于对照组(P<0·05);骨代谢生化指标结果显示,吗啡组大鼠血清钙和尿钙以及TRAP、HOP较对照组增加显著(P<0·05)。结论:长期使用吗啡对下丘脑-垂体-卵巢轴及骨组织会有不同程度的损伤。     

吡咯列酮对PCOS大鼠下丘脑、卵巢中瘦素受体表达的影响及其意义

目的:研究吡咯列酮对PCOS大鼠下丘脑、卵巢中瘦素受体(Lep-R)表达的影响及其意义。方法:将30只雌性SD大鼠分为3组:正常对照组、PCOS组、吡咯列酮干预组。放射免疫法测定各组大鼠血清T、LH、空腹血清血糖(fasting serum glucose,FSG)、胰岛素(insulin,Ins)、瘦素(leptin,Lep)水平,通过免疫组织化学、实时荧光相对定量PCR(Real-time RT-PCR)方法检测各组大鼠下丘脑、卵巢中Lep-R的相对表达。结果:经吡咯列酮干预后,PCOS大鼠血清T、LH、Ins、Lep水平明显降低,下丘脑Lep-R表达增强,而卵巢中Lep-R表达减弱。结论:下丘脑Lep-R表达的下调可能是PCOS大鼠瘦素抵抗的原因之一;吡咯列酮可以改善PCOS大鼠内分泌紊乱。     

来曲唑治疗大鼠子宫内膜异位症模型作用及机制的研究

目的:探讨第3代芳香化酶抑制剂(aromatase inhibitors,AIs)来曲唑治疗大鼠子宫内膜异位症模型的效果及作用机制。方法:用自体子宫内膜移植方法建立大鼠内异症模型,随机将20只建模成功大鼠分为来曲唑组和盐水对照组,比较治疗前后EM大鼠异位病灶体积的变化;免疫组化法检测异位内膜病灶中细胞色素P450芳香化酶(P450arom)、环氧合酶-2(COX-2)、血管内皮生长因子(VEGF)、增殖细胞核抗原(PCNA)蛋白的表达;末端转移酶介导的缺口末端标记法(TUNEL)检测细胞凋亡情况;放射免疫分析法测定大鼠血清FSH、LH、E2水平。结果:来曲唑组异位病灶体积缩小(P<0.01);异位内膜中P450arom、COX-2、VEGF、PCNA蛋白表达与对照组相比均明显降低(P<0.05);来曲唑组异位内膜细胞凋亡率较对照组明显增加(P<0.01);两组大鼠血清FSH、LH、E2水平无明显差异(P>0.05)。结论:来曲唑治疗大鼠子宫内膜异位症模型有效。来曲唑通过降低异位内膜局部P450arom、COX-2、VEGF蛋白表达及抑制异位内膜增殖并促进凋亡发挥治疗子宫内膜异位症的作用。来曲唑对大鼠血清FSH、LH、E2水平无明显影响。     

经腹鞘内子宫三角形切除术21例临床分析

目的:比较传统全子宫切除术与经腹鞘内子宫三角形切除术术后恢复情况及对性激素的影响。方法:选择行经腹鞘内子宫三角形切除术21例患者为观察组,选择同期采用传统全子宫切除术切除子宫的21例患者作对照组,观察两组术后恢复情况,术前、术后3、6月血清FSH、LH、E2含量的变化情况。结果:观察组术后病率明显降低(P<0.05);观察组术前、术后血清FSH、LH、E2含量差异无统计学意义(P>0.05)。观察组术后FSH、LH含量较对照组低(P<0.05),E2含量较对照组高(P<0.01)。结论:经腹鞘内子宫三角形切除术术后恢复好,对卵巢功能影响小。     

免疫抑制剂FK506对雌性大鼠性腺轴的影响

目的:探讨免疫抑制剂FK506对雌性大鼠生殖内分泌功能的影响。方法:将Wistar大鼠随机分为4组:对照组、低剂量组、中剂量组和高剂量组,分别每日给予生理盐水以及不同剂量FK506灌胃(0.2mg/kg、1mg/kg、2mg/kg)×42d。用药前2周及用药期间每日行阴道涂片检查,观察大鼠动情周期变化;停药后于动情间期处死大鼠,放免法检测血清E2、P、LH水平,免疫组化法检测卵巢、垂体、下丘脑雌激素受体(ER)表达水平。结果:①连续给药42d后,中、高剂量组大鼠动情周期平均天数(5.0d、5.5d)均较对照组(4.1d)显著延长(P<0.05,P<0.01)。②中、高剂量组大鼠平均血清孕酮(P)水平(42.5ng/ml、32.8ng/ml)与对照组(78.9ng/m)相比较明显降低(P均<0.01)。低、中、高剂量组大鼠平均血清雌二醇(E2)水平(9.4pg/ml,7.7pg/ml,8.3pg/ml)也明显低于对照组(14.3pg/ml)(P均<0.05)。各组间黄体生成素(LH)水平无显著差异。③大鼠卵巢、垂体以及下丘脑组织中雌激素受体表达与FK506剂量呈负相关。结论:大鼠用药后血清P及E2水平明显下降,性腺轴各组织器官ER表达也发生不同程度下调,上述作用呈一定的量-效关系。提示FK506长期用药对大鼠生殖内分泌功能可造成一定程度的影响。     

雄激素致不孕大鼠胰腺、下丘脑及卵巢雄激素受体mRNA表达

目的:研究雄激素致不孕大鼠(ASR)胰腺、下丘脑及卵巢组织中雄激素受体(AR)mRNA的含量变化。方法:9日龄SD雌性大鼠皮下注射丙酸睾丸酮制备ASR模型,于106日龄左右(动情前期)处死,取血放免法测定△4-雄烯二酮(△4-A)、总睾酮(TT)、游离睾酮(FT)、胰岛素(Ins)和C-肽(C-P),提取胰腺、下丘脑及卵巢总RNA,以单碱基突变模板为内对照的RT-PCR方法对ARmRNA进行定量分析。结果:ASR模型血△4-A、TT、FT、Ins、C-P均显著高于对照组(P<0.05,P<0.01),胰腺、下丘脑及卵巢的AR mRNA表达水平明显升高,与对照组相比差异有统计学意义(P<0.05,P<0.01)。结论:ASR模型血雄激素水平升高,上调胰腺、下丘脑及卵巢AR mRNA的表达,引起该模型的高胰岛素血症和无排卵。     

莉芙敏对去卵巢大鼠下丘脑视前区5-HT1AR和5-HT2AR表达的影响

目的:观察去卵巢大鼠应用黑升麻异丙醇提取物--莉芙敏(ICR)治疗1-4周后,免疫组化方法检测5-羟色胺1A受体(5-HT1AR)和5-HT2AR在大鼠下丘脑视前区表达的变化情况,为莉芙敏缓解围绝经期潮热症状的机制研究提供形态学依据.方法:雌性大鼠分为假手术组(Sham组)、去卵巢组(OVX组)、OVX后戊酸雌二醇治疗(OVX+E2)组和OVX后ICR治疗(OVX+ICR)组,每组40只.所有大鼠术后恢复2周后,再用相应的药物分别治疗1,2,3,4周,麻醉,心脏灌注,取脑,制作冰冻切片.免疫组化法观察各组大鼠下丘脑视前区5-HT1AR和5-HT2AR的表达.结果:①OVX组1-4周时大鼠下丘脑视前区5-HT1AR阳性细胞数量和吸光度均较同期Sham组增加;ICR和戊酸E2治疗1-4周后,OVX+E2组和OVX+ICR组大鼠下丘脑视前区室周带表达5-HT1AR的阳性细胞数量和吸光度均较同期OVX组减少.②下丘脑视前区中间带和外侧区5-HT2AR阳性细胞数量和吸光度的变化:OVX组大鼠,1-4周均较同期Sham组增加;ICR和戊酸E2治疗1周和2周后,OVX+E组和OVX+ICR组较同期OVX组增加;治疗3周和4周后,OVX+E2组和OVX+ICR组均较同期OVX组减少.结论:5-HT1AR和5-HT2AR在去卵巢大鼠下丘脑视前区的表达量均增加;ICR和戊酸E2治疗后,5-HT1AR在大鼠下丘脑视前区的表达量减少,而5-HT2AR在下丘脑视前区的表达先增多后减少.ICR可能通过调节下丘脑视前区体温调节中枢的5-HT1AR和5-HT2AR的表达,以缓解围绝经期的潮热症状.     

子宫肌瘤患者子宫切除术后卵巢功能的改变

目的探讨不同年龄的子宫肌瘤患者全子宫或次全子宫切除术后卵巢功能的改变.方法选择100例子宫肌瘤患者随机分3组,Ⅰ组30例(34～40岁),行次全子宫切除;Ⅱ组30例(34～40岁),行全子宫切除;Ⅲ组40例(＞40～42岁)行全子宫切除.另同时选择健康女性40例作为对照组.手术组分别于术前,术后测血卵泡刺激素(FSH)、雌二醇(E2)并记录有无更年期症状出现.对照组同期随访2年.结果术后按要求完成24个月随访的共70例,术后3～12个月各组E2、FSH水平与术前相比无差异.术后24个月Ⅰ组与Ⅱ组E2、FSH水平与术前相比无差异,Ⅲ组E2、FSH水平术前与术后3～12个月相比有差异(P＜0.05).Ⅲ组术后24个月时更年期症状的发生率明显高于Ⅰ、Ⅱ组患者的同期发病率(P＜0.01).对照组完成2年随访,与Ⅰ、Ⅱ组血FSH、E2水平及更年期症状的发生率比较无差异(P＞0.05).结论40岁以前子宫肌瘤患者无论是次全或全切子宫后2年内卵巢功能无改变;而＞40～42岁者术后2年卵巢功能有改变,且可提前出现更年期症状.     

胰岛素抵抗及子宫内膜增殖大鼠模型中脂肪因子和PI3K/AKT信号通路相关蛋白的表达

目的:观察有胰岛素抵抗及子宫内膜增殖大鼠模型中血浆脂联素(Adipo)等脂肪因子的水平,检测Adipo和脂联素受体(AdipoR)在大鼠子宫组织中的表达,并探讨其分子生物学机制。方法:选取8周龄Sprague-Dawley(SD)大鼠45只(每组9只),分别给予普通饮食(StD组)和高脂饮食(HFD组)40周。将StD组分为对照C组(普通饮食+假去势手术+对照溶剂)、NO组(普通饮食+去势手术+对照溶剂)、NE组(普通饮食+去势手术+17β-雌二醇灌胃),HFD组分为FO组(高脂饮食+去势手术+对照溶剂)和FE组(高脂饮食+去势手术+17β-雌二醇灌胃)。应用酶联免疫吸附(ELISA)检测小鼠血浆中脂肪因子水平,实时荧光定量PCR、Western Blotting和免疫组化检测子宫内膜中脂肪因子的水平,免疫组化检测子宫内膜中PTEN、AMPK和PI3K/AKT信号通路相关蛋白的表达。结果:①与NE组大鼠相比,FE组大鼠子宫腔上皮细胞和腺上皮细胞的高度、肌层的厚度显著增加(P<0.05)。②与对照C组相比,子宫内膜增生组(NE组和FE组)大鼠血浆Adipo水平显著降低(P<0.05),FO组大鼠血浆Adipo显著升高(P<0.05)。③在雌激素的作用下(NE组和FE组)子宫组织中Adipo mRNA的表达增多:与NO组大鼠相比,NE组大鼠子宫组织中Adipo mRNA水平显著升高(P<0.05);与FO组大鼠相比,FE组大鼠Adipo mRNA水平也显著升高(P<0.05)。大鼠子宫中AdipoR1 mRNA和AdipoR2 mRNA水平在各组之间差异无统计学意义(P>0.05)。与对照C组相比,FE组大鼠子宫组织中Adipo蛋白的表达明显降低(P<0.05)。④FE组子宫PTEN和p-AMPK蛋白的表达显著低于对照C组(P<0.05),PI3Kp85α、p-AKT蛋白表达显著高于对照C组(P<0.05)。结论:长期高脂饮食诱导大鼠的胰岛素抵抗可协同17β-雌二醇刺激子宫内膜增殖;胰岛素抵抗和雌激素影响血浆Adipo的水平;胰岛素抵抗和雌激素的协同作用使大鼠子宫内膜PTEN的表达降低、AMPK通路可能被抑制、PI3K/AKT信号通路可能被激活。     

Changes in the reproductive endocrine function in rat following intraovary microinjection of inhba overexpression lentivirus vectors

Abstract

Objective: To investigate the reproductive endocrine changes after inhba overexpression into rat ovary.

Method: Thirty Sprague-Dawley rats were randomly assigned to three groups. Inhba overexpression lentivirus vectors (LV-eGFP-inhba) were microinjected into rat ovary (INH group); Control animals received the same amount lentivirus vector empty (CON group) or LV-eGFP (GFP group). Antral follicle amount and diameter were counted and serum level of activin A, E2, P, FSH, and LH and the expression of ER-α, ER-β, PR, FSHR, and LHR were measured.

Results: There was no significant difference among three groups in antral follicle amount; antral follicle diameter was increased in INH group rats compared with the other group rats. Serum levels of activin A, E2, P, and FSH were increased and LH was decreased in INH group rats compared with the other group rats. The mRNA and protein expression of ER-α, ER-β, FSHR was higher in INH group rats than that in the other group rats. There was no significant difference in mRNA and protein expression of PR among the three group rats, LHR expression was decreased in INH group rats compared with the other two group rats.

Conclusion: inhba overexpression in rat ovary in vivo may change reproductive endocrine function.     

中药补肾调冲方对卵巢早衰大鼠激素水平和卵巢Bcl-2/Bax表达的影响

目的:探讨补肾调冲方对雷公藤多苷片(GTW)致卵巢早衰(POF)的治疗作用。方法:雌性SD大鼠42只,随机分为正常组、模型组、结合雌激素片(雌激素组)和补肾调冲方治疗高、中、低剂量组。运用酶联免疫吸附试验(ELISA)法检测血清中雌二醇(E_2)、卵泡刺激素(FSH)、抑制素B(INHB)水平。Western blotting法和RT-PCR法检测卵巢组织中Bcl-2、Bax蛋白及mRNA的表达水平。结果:正常组和各给药组E_2的含量均高于模型组(P0.01)。正常组和各给药组FSH含量均低于模型组(P0.01);正常组和各给药组INHB含量均高于模型组(P0.01)。低剂量组INHB的含量与雌激素组比较,差异有统计学意义(P0.05)。模型组大鼠卵巢中Bcl-2蛋白和mRNA水平的表达显著低于正常组(P0.05);各给药组Bcl-2蛋白和mRNA水平的表达显著高于模型组(P0.01)。模型组大鼠卵巢中Bax蛋白和m RNA水平的表达显著高于正常组(P0.05);各给药组Bax蛋白和mRNA水平的表达显著低于模型组(P0.01)。低剂量组Bax蛋白的表达与雌激素组比较,差异有统计学意义(P0.05)。结论:中药补肾调冲方对卵巢性激素水平具有调节作用,能提高卵巢对性激素的敏感性,促进卵巢排卵;通过上调Bcl-2和下调Bax的表达,抑制卵巢中颗粒细胞的过度凋亡,减少卵泡闭锁,促进卵巢功能的恢复。     

绝经妇女血浆一氧化氮、内皮素的水平及补充性激素后的变化

目的 探讨绝经妇女雌激素下后血浆一氧化氮（ＮＯ）与内皮素（ＥＴ）水平的变化，及服用结合雌激素加安宫黄体酮对ＮＯ、ＥＴ水平的影响。方法 选择７０例绝经妇女作为绝经组，２８例有围绝经期症状的妇女作为围绝经组，２６例月经周期正常的妇女作为正常月经组。绝经组中３０例服用结合雌激素加安宫黄体酮者为绝经１组，另外２０例服用碳酸钙治疗者为绝经２组，绝经１期及绝经２组用药时间均为６个月。以上各组均取静脉血测定ＮＯ     

Blood levels of estradiol, FSH and LH in women with climacteric syndrome--conjugated estrogen therapy

To study the types of patients with climacteric syndrome who respond to conjugated estrogen therapy, we investigated the results of 1- to 2-month therapy in 52 patients by comparing their pre- and post-drug level of blood estradiol (E2), FSH and LH as well as comparing information through a questionnaire on menopausal complaints listed according to Kupperman. Predrug E2 in the patients studied was lower than normal, but the lowering was not significantly specific to any particular climacteric symptom. Blood FSH was higher in the patients complaining of hot flushing, sweating, depression, feeling of something sticking in the throat, and decreased sexual desire, whereas blood LH was higher in the patients with hot flushing and sweating. Changes in various symptom were investigated in relation to hormonal changes found after conjugated estrogen therapy. In the patients whose E2 was increased and FSH and LH were decreased after the therapy, hot flushing, cold sensation, excitability and insomnia were ameliorated at a high rate. Numbness was favorably treated in the patients responding with increased E2, whereas shoulder stiffness, fatigability and headache was reduced in those responding with decreased LH.     

C-AMP concentration in various organs of female rats and in human ovaries with aging (author's transl)

The change in 3',5'-cyclic adenosine monophosphate (c-AMP) concentration was observed in various organs of rats in gonadal cycle in adult group and with aging (30, 70, 100, 120 weeks), and in human ovaries with aging. 1) The average c-AMP concentration of ovaries of rats showed a significant change with estrus cycle and was higher in the following sequence: proestrus, diestrus II, diestrus I and estrus phase. This tendency was also seen in hypothalamus and pituitary, but was not statistically significant, 2) The average c-AMP concentration in tissues began to decline significantly from 70 weeks in cerebral cortex and hypothalamus, and from 80 weeks in ovaries. However, on the other hand the concentrations in pituitary, liver and adrenal declined markedly from 100 weeks. 3) The c-AMP in ovaries of 80 weeks rats by pregnant mare serum (PMS) road increased by 0.5-fold in concentration, and by 0.6-fold in whole tissue relative to that of 30 weeks rats. 4) A significant difference in serum LH and FSH level between ovarian artery and vein was not found in cycling mature group, non-cycling climacteric group and post-menopausal group of women. 5) Both average concentrations and total values of c-AMP in ovaries of non-cycling climacteric and post-menopausal women were lower than those of mature cycling women. This fact may imply a different response by ovarian tissues such as corpus luteum, follicle and other tissues to gonadotropin. From these results of c-AMP in tissues, it is concluded that the decline of ovarian function with aging of rats was relatively earlier than pituitary, although being delayed compared with hypothalamus, and were the ovarian function in humans declined in the premenopausal period.     

SUMEVA, a new system of climacteric symptom evaluation, and its correlation with FSH and estradiol levels

OBJECTIVE: To evaluate a new climacteric symptom scale (SUMEVA) and to assess its correlation with follicle stimulating hormone (FSH) and estradiol (E2) levels. METHODS: 115 healthy perimenopausal women who were not receiving, nor had received, hormone therapy were studied. They were asked to complete 3 questionnaires concerning climacteric symptoms: (1) Kupperman's index (KI), (2) Green scale (GS), and (3) SUMEVA, which is the sum of symptom evaluations done in an analog visual scale. FSH and E2 determinations were done by chemoluminiscence. Statistical analysis: The comparison among the groups was done by Student's t test. Pearson correlation analysis was done between FSH and E2 levels and KI, the GS, and SUMEVA. RESULTS: There were 60 women with FSH < or = 30 mIU/mL (group I) and 55 with FSH > 30 mIU/mL (group II). The KI average in the whole group was 13.2 +/- 8.1, the GS 20.6 +/- 13.1, and the SUMEVA 65.6 +/- 44.9. The three scales had a significant correlation between them. CONCLUSIONS: No correlation of KI, GS, or SUMEVA was found with FSH and E2 levels, but the SUMEVA was as effective as the other previously validated, scales for climacteric symptom evaluation.     

Expression of mitochondria-dependent apoptosis genes (p53, Bax, and Bcl-2) in rat granulosa cells during follicular development

OBJECTIVE: We examined rat ovarian granulosa cells at different follicular stages and evaluated the apoptosis pattern of the mitochondria-dependent genes during folliculogenesis. METHODS: After down-regulating ovarian function with gonadotropin-releasing hormone agonist (GnRHa), granulosa cells were collected from the rat ovary at different stages of the following different hormonal treatment paradigms: stage E (after estrogen treatment), EF (after E + follicle-stimulating hormone [FSH] treatment), and EF hCG (after E + FSH + human chorionic gonadotropin treatment). To evaluate the in vitro susceptibility of granulosa cells at different developmental stages to apoptosis, the collected cells were cultured in a serum-free medium with or without E2 for 24 hours. The regulation of apoptosis in the granulosa cells was analyzed using fluorescein-activated cell sorting, quantitative competitive polymerase chain reaction, and western blot methods. RESULTS: The apoptosis rate of the freshly isolated granulosa cells tended to increase according to the hormonal treatment paradigm. In addition, during the hormone treatment, mitochondria-dependent apoptosis genes showed the following changes: although the Bax mRNA level did not change, the Bcl-2 mRNA level decreased significantly (P <.05). The p53 mRNA level increased significantly (P <.05) and closely matched the apoptosis rate (R = 0.7, P <.05). The expression of the active form of the caspase-3 protein (the final executioner of cell death) tended to increase and showed a good correlation with the apoptosis rate (R = 0.96, P <.01). After an in vitro culture of the granulosa cells, the apoptosis rate tended to increase at all stages, particularly stage EF hCG (P <.05). Bax and p53 mRNA tended to increase and showed a good correlation with the apoptosis rate (R = 0.64, P <.05 and 0.86, P <.01). The Bcl-2 mRNA level tended to decrease at all stages showing no correlation with the apoptosis rate. The expression level of the active caspase-3 protein tended to increase at all stages and showed a good correlation with the apoptosis rate (R = 0.93, P <.01). CONCLUSION: Apoptosis of rat ovarian granulosa cells tends to increase according to the stage of follicular development. Among the mitochondria-dependent genes, p53 closely correlates with granulosa cell apoptosis during follicular development.     

GnRHa联合雌激素预防顺铂致小鼠卵巢功能损伤的保护作用

目的:研究促性腺激素释放激素激动剂(GnRHa)联合雌激素(E2)对顺铂(CDDP)所致小鼠卵巢功能损伤的保护作用。方法:选择具有正常性周期的5～6周龄雌性Balb/c小鼠40只,随机分为正常对照组、CDDP组、GnRHa+E2组、GnRHa+E2+CD-DP组,分别注射生理盐水、CDDP、GnRHa+E2和GnRHa+E2+CDDP。采用放免法测定各组小鼠血清中卵泡刺激素(FSH)、E2水平。在停药后间期处死小鼠,卵巢称重后组织病理切片HE染色观察各组卵巢组织结构及卵泡数量变化。结果:CDDP组小鼠与Gn-RHa+E2+CDDP组比较,血清FSH明显升高,E2水平明显降低(P0.05)。CDDP组卵巢和子宫湿重明显低于GnRHa+E2+CDDP组(P0.05)。CDDP组与其他3组比较,卵巢卵泡总数最少(P0.05)。经统计学分析,CDDP与GnRHa+E2间有交互作用。结论:GnRHa联合雌激素能够减轻顺铂对卵巢结构及功能的破坏,在一定程度上保护卵巢的储备功能。