电针对下丘脑-垂体-性腺轴的调节

下丘脑-垂体-性腺轴是哺乳动物生殖及生长发育过程中重要的调控中枢。低频、低电流强度的连续波电针刺激作用于一些根据中医传统理论或现代医学神经节段分布理论选择的穴位后，可对下丘脑-垂体-性腺轴产生显著的双向调节作用。其机理可能是电针可有效刺激中枢及外周脏器、组织中的某些物质的合成和释放，提高低激素状态水平或降低高激素状态水平的性激素浓度。但这种双向调节作用的机制特别是对下丘脑-垂体-睾丸轴的调控机制还有待更深入的研究。     

电针对下丘脑-垂体-性腺轴的调节

下丘脑-垂体-性腺轴是哺乳动物生殖及生长发育过程中重要的调控中枢.低频、低电流强度的连续波电针刺激作用于一些根据中医传统理论或现代医学神经节段分布理论选择的穴位后,可对下丘脑-垂体-性腺轴产生显著的双向调节作用.其机理可能是电针可有效刺激中枢及外周脏器、组织中的某些物质的合成和释放,提高低激素状态水平或降低高激素状态水平的性激素浓度.但这种双向调节作用的机制特别是对下丘脑-垂体-睾丸轴的调控机制还有待更深入的研究.     

二硫化碳对雄性大鼠下丘脑-垂体-性腺轴分泌功能的影响及NO的干预作用

目的探讨二硫化碳（CS2）对雄性大鼠下丘脑-垂体-性腺轴（hypothalamic—pituitary-gonad axis,HPGA）分泌功能的影响,同时观察一氧化氮（NO）对其的干预作用。方法清洁级SD雄性大鼠36只随机分为6组,以不同浓度CS2（0、50、250、1250mg／m3）静式吸入染毒,共10周,另设CS2（1250mg／m3）＋SNP（5mg／kg）组和CS（1250mg／m3）＋L—NMMA（2mg／kg）组,染毒结束前10d,对CS2高剂量染毒的3个组分别进行腹腔内注射生理盐水（NS）、SNP及L—NMMA,染毒结束后,测定大鼠血清、下丘脑、垂体、睾丸中NOS活性及NO含量,采用放射免疫法检测血清Gn—RH、FSH、LH、T的含量。结果（1）随着CS2染毒剂量的增加,大鼠血清、下丘脑、垂体、睾丸中NOS与iNOS活性、NO含量与对照组相比较均有不同程度的降低和减少;加入SNP后,NOS活性、iNOS活性均有所增高,与高剂量组相比较差异具有统计学意义（P〈0．05）,NO含量均有所增加,但差异无统计学意义（P〉0．05）;加入L－NMMA后N0s活性、iNOS活性降低、NO含量减少,但与高剂量组比较无统计学意义（P〉0．05）。（2）随着CS2染毒剂量的增加,血清中GnRH、LH的含量均有所下降,FSH含量随着染毒剂量的增加而增加,T有先升高后降低的趋势。加入SNP后,血清中GnRH、LH及T含量均有所升高,且与高剂量组比较具有统计学意义（P〈0．05）,FSH含量变化不明显（P〉0．05）．加入L—NMMA后,血清中GnRH、LH及T含量均有所降低,FSH含量变化不明显,与高剂量组比较均无统计学意义（P〉0．05）。结论（1）CS2染毒对大鼠体内N0含量有一定的影响;（2）CS2染毒能影响大鼠HPGA分泌的性激素有影响,NO对其具有一定的干预作用。     

下丘脑-垂体-肾上腺皮质轴与多巴胺系统的相互调节作用

研究表明下丘脑-垂体-肾上腺皮质(hypothalamic-pituitary-adrenal,HPA)轴和多巴胺(dopamine,DA)系统与某些神经相关疾病存在关联,HPA轴通过不同途径和机制来调节多巴胺系统,影响脑内多巴胺的生物学功能,而多巴胺系统也能调节HPA轴功能。本文围绕HPA轴和DA系统的相互调节作用在维系中枢神经系统功能中的重要作用进行综述。     

早期应激事件与下丘脑-垂体-肾上腺轴的发育

早期应激事件对下丘脑-垂体-肾上腺轴的远期发育产生影响。同时,这种影响又受到多种因素的调节。大量实验证明早期应激发生的时间,应激性质以及后代性别都参与决定远期下丘脑-垂体-肾上腺轴的发育方向。下面围绕这几个方面进行综述。     

下丘脑-垂体-肾上腺轴昼夜节律指标随青春期发育变化的特征

目的 描述下丘脑-垂体-肾上腺（HPA）轴昼夜节律指标随青春期发育变化的特征。方法 2015年10月选择安徽省马鞍山市3所小学1 070名2~3年级学生为研究对象,并于2016年和2017年开展随访调查。调查内容包括体格发育、青春期发育和HPA轴昼夜节律。收集清晨觉醒时、醒后30 min和晚上入睡时3个时点唾液样本,并计算HPA轴昼夜节律指标：皮质醇觉醒应答（CAR）、昼间皮质醇总分泌量及昼夜皮质醇斜率（DCS）。采用睾丸容积、乳房发育分别评价男女童青春期发育阶段。采用问卷调查收集出生日期、入睡与起床时间和每周体力活动等信息。采用非参数检验比较HPA轴昼夜节律基线各指标在基线、随访期及不同青春期发育进程中的差异。结果 随访期间,青春期发育启动组和持续发育组CAR值、CAR变化值均高于与持续未发育组,差异有统计学意义（CAR：Z值分别为8.551和4.680,均P<0.01;CAR变化值：Z值分别为4.079和2.700,均P<0.01）;青春期启动组昼间皮质醇总分泌量高于持续未发育组,差异有统计学意义（Z=2.591,P=0.010）。与持续未发育组相比,DCS变化值在青春期启动组和持续发育组中下降明显,差异有统计学意义（Z=-2.450,Z=-2.151;均P<0.05）。昼间皮质醇总分泌量变化值与DCS在不同青春期发育进程组儿童中差异无统计学意义（昼间皮质醇总分泌量变化值：χ²=2.747,P=0.253;DCS：χ²=4.554,P=0.032）。结论 HPA轴昼夜节律指标与青春期发育有关,CAR、昼间皮质醇总分泌量随青春期发育进行而升高,昼间皮质醇差值随青春期发育而下降。     

CS_2吸入染毒对雄性大鼠下丘脑-垂体-性腺轴超微结构的影响及NO干预作用

[目的]探讨二硫化碳（CS2）对雄性大鼠下丘脑-垂体-性腺轴超微结构的影响及一氧化氮（NO）的干预作用。[方法]将24只雄性SD大鼠按体重随机分为4组：对照组、CS2染毒组、硝普钠（sodium nitroprusside,SNP）干预组和N-甲基-L-精氨酸（L-NMMA）干预组。除对照组外,其余3组均以1250mg/m3CS2进行静式吸入染毒,2h/d,5d/周,共10周,SNP和L-NMMA干预组在动物染毒结束前10d开始分别腹腔注射SNP（5mg/kg）和L-NMMA（2mg/kg）,1次/d。染毒结束后,取下丘脑、垂体和睾丸组织,利用透射电子显微镜观察组织超微结构的改变。[结果]CS2染毒可造成下丘脑神经元、垂体促性腺激素细胞、生长激素细胞和睾丸支持细胞线粒体肿胀,内质网扩张,SNP对CS2引起的下丘脑、垂体、睾丸组织的损伤具有拮抗作用,而L-NMMA则进一步导致病变的发生。[结论]CS2可造成下丘脑、垂体和睾丸组织超微结构的改变,NO在此过程中发挥重要作用。     

氟对暴露人群下丘脑-垂体-性腺轴激素水平的影响

目的探讨氟对成人下丘脑-垂体-性腺轴生殖激素水平的影响。方法选择水氟浓度为3.89mg/L的开封孙营村为调查区,另选水氟浓度小于1.0mg/L的沈李楼村作为对照区。对两区居住5年以上全部居民进行健康体检,并测定尿氟含量。随机抽取空腹静脉血150份,应用放射免疫方法测定血清促性腺激素释放激素(GnRH)、促黄体生成素(LH)、睾酮(T)和雌二醇(E2)水平。结果高氟区水氟、土壤氟和粮食氟含量均高于对照区(P0.05),且高于国家标准;空气氟两地区均未检出。高氟区人均日摄氟量高于对照区(P0.05),且高于国家标准。高氟区人群尿氟含量明显高于对照区(P0.05)。高氟区男性、女性血清GnRH水平与对照区比较差异均无显著性。高氟区男性血清LH水平明显高于对照区(P0.05),女性血清LH水平与对照区比较,差异无显著性。高氟区男性血清T水平明显低于对照区(P0.05),而女性血清T水平则明显高于对照区(P0.05)。高氟区男性、女性血清E2水平与对照区比较差异均无显著性。结论氟能影响成人下丘脑-垂体-性腺轴各层面生殖激素水平,因而表现出生殖内分泌干扰作用,且对男性的影响大于女性。     

Attractin基因敲除鼠下丘脑-垂体-睾丸轴组织学的观察

目的:观察Attractin基因敲除雄鼠下丘脑、垂体、睾丸等器官的组织学改变。方法:取Attrac-tin基因功能丧失的雄鼠和正常雄鼠各6只分成实验组和对照组,颈椎脱臼处死后迅速取其下丘脑、垂体、睾丸和附睾组织固定,石蜡包埋,并制做HE切片。结果:Attractin基因功能丧失的雄鼠下丘脑和垂体HE切片发现明显的海绵状变性。睾丸和附睾HE切片未发现明显改变。结论:Attractin基因功能的丧失能引起雄鼠下丘脑和垂体的海绵状变性,但未引起睾丸和附睾明显的组织学改变。     

乳房早发育患儿下丘脑—垂体—性腺轴功能检测及其临床意义

乳房早发育是儿科较常见的内分泌疾患,目前病因尚不清楚,既往认为属良性自限性疾病,最近有报道部分病人可发展成中枢性性早熟［１］。本文通过检测乳房早发育患儿ＬＨＲＨ激发试验前后ＬＨ、ＦＳＨ值,并与部分性腺早熟及中枢性性早熟患儿对照,进一步探讨乳房早发育患儿的发病机理及其检测指标在临床的应用价值。１　对象与方法１．１　研究对象　①乳房早发育组：按Ｗｉｌｋｉｎｓ标准［２］诊断为乳房早发育患儿２０例,年龄２岁半～７岁２月,平均（５．８±１．２）岁。②部分性腺早熟组：乳房发育伴骨龄提前１０例,年龄２岁８月～…     

Effect of progestin-only pill on pituitary-ovarian axis activity during lactation

We have monitored effects of progestin-only pill (POP) on ovarian activity during breastfeeding. Twenty-one women, using barrier methods (BM) of contraception and 9 women on POP were enrolled 6 weeks postpartum (PP) and followed-up to 18 weeks PP. There was little change in plasma follicle-stimulating hormone and luteinizing hormone, and no differences between BM and POP. POP did not affect plasma estradiol. There was no difference between BM and POP in plasma inhibin B concentrations. The size of follicles was similar in both groups in all time points. There was an increase in the endometrial thickness from 6 weeks PP to 18 weeks PP in BM (3.7 ± 0.5 vs. 5.4 ± 0.6 mm, p < 0.05), but no differences within the POP group or between the treatment groups. POP does not suppress gonadotropins nor affect growth of ovarian follicles during breastfeeding. Thus, the contraceptive effect of POP is likely mediated through local actions at the endometrium and cervix in a manner similar to that in menstruating women.     

Kisspeptin与早期不明原因流产的相关性研究

目的通过检测孕早期母体血清Kisspeptin水平和绒毛组织的表达,拟探讨其在妊娠中的作用。方法采用免疫组织化学方法分析正常妊娠组(20例)和自然流产组(20例)绒毛组织中Kisspeptin的表达水平;采用酶联免疫吸附法(ELISA)检测孕5~10周妇女(40例)血清Kisspeptin浓度。结果①免疫组织化学分析显示,Kisspeptin在正常妊娠组[灰度值(170.3±7.134)]的表达显著高于自然流产组[灰度值(198.4±5.699))。②ELISA法结果显示,正常妊娠组Kisspeptin在血清中的浓度随孕周增大而增高,自然流产组Kisspeptin在血清中的浓度随孕周逐渐降低。结论Kisspeptin在孕早期胚胎着床及发育过程中起着重要作用,可作为一种预测妊娠结局的指标。     

Kisspeptin recombinant oral vaccine: A master gene vaccine inhibiting the reproductive physiology and behavior of ram lambs

The KISS1 gene product, kisspeptin, stimulates gonadotrophic steroid hormone (GNRH) neuronal signaling through the G-protein coupled receptor, kiss1r. Disturbance of this signaling pathway causes hypogonadotropic hypogonadism in mammals. As part of this cutting-edge research project, we analyzed the efficacy of an oral kisspeptin recombinant vaccine on the reproductive physiology and behavior of ram lambs. Ten 56-day old ram lambs were randomly divided into treatment and control groups to receive the experimental recombinant vaccines, C500/pKS-asd or C500/pVAX-asd (aspartate-β semialdehyde dehydrogenase), respectively. The vaccines were orally administered at day 0, 28 and 56 and blood samples were taken and scrotal circumference data recorded at 14-day intervals (days 0, 14, 28, 42, 56, 70, and 84). At the end of the experimental period, day 98, sexual behaviors were assessed, scrotal circumferences were measured, and blood samples were collected. Testicular samples were also collected after the animals were sacrificed. Anti-kisspeptin antibody and testosterone serum levels were measured by indirect ELISA. Results demonstrated that the levels of anti-kisspeptin antibodies were significantly higher in the treatment group compared to controls (P < 0.05, P < 0.01 and P < 0.001). However, serum testosterone levels were lower in the treatment group (P < 0.01). Interestingly, vaccine administration contributed to a significant reduction (P < 0.01) in sexual behavior propensity. These results suggest that the kisspeptin recombinant oral vaccine regulates and inhibits the reproductive physiology and behavior of ram lambs.     

探讨育阴灵加减治疗肝肾阴虚型卵巢早衰的临床疗效及其对下丘脑-垂体-卵巢轴的调节作用

目的探讨育阴灵加减治疗肝肾阴虚型卵巢早衰的临床疗效及其对下丘脑-垂体-卵巢轴的调节作用。方法将肝肾阴虚型卵巢早衰患者52例随机分为观察组与对照组各26例,观察组以育阴灵加减治疗,对照组采用人工周期法治疗,疗程为3个月。比较两组患者临床症状改善情况,两组治疗前、后血清卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E_2)水平变化。结果观察组治疗后临床总有效率88.5%较对照组的73.1%明显提高,差异有统计学意义(P0.05);与治疗前比较,两组治疗后中医症状积分均明显降低,差异均有统计学意义(P0.05);与对照组比较,观察组治疗后中医症状积分明显降低,差异有统计学意义(P0.05)。治疗后两组患者血清E_2明显提高,FSH、LH明显降低,与治疗前比较差异有统计学意义(P0.05);观察组血清E_2、FSH、LH改善程度明显优于对照组,差异有统计学意义(P0.05)。结论育阴灵加减通过调节患者下丘脑-垂体-卵巢轴功能,对肝肾阴虚型卵巢早衰具有较好的治疗作用,值得临床推广应用。     

Potent effect of KISS1-54 DNA vaccine compared with KISS1-10 DNA vaccine in inhibiting the fertility of female rats

BackgroundMost studies on immunocastration currently focused on male animals. However, immunization of male animals does not completely inhibit sexual behavior and fertility. This study aimed to compare the immunocastration effect of KISS1 DNA vaccines encoding different lengths of kisspeptins in female rats for effective castration effects on both male and female rats.MethodsFifteen female rats were randomly divided into three groups. The rats in T1 group or T2 group was orally given respectively KISS1-54 or KISS1-10 DNA vaccines with fused tPA signal peptide, and the control group (Group C) was orally administered with empty vector vaccine, at a dose of 5 × 10⁹ CFU/rat at weeks 0, 3 and 6 of the study. Blood samples were collected by retroorbital bleeding before primary immunization and at weeks 3 and 9 after primary immunization.ResultsBoth KISS1-54 and KISS1-10 DNA vaccines induced the body’s humoral immune response, and the anti-kisspeptin antibody titres in the T1 group were significantly higher than that in T2 and C groups (p < 0.05). The rats in T1 group has lower serum kisspeptin and estradiol levels than those in T2 and C groups and smaller litter size of rats than those in the control group after mating (p < 0.05). No significant difference was observed between T2 and C groups. The levels of KISS1 and GPR54 mRNA in the hypothalamus and ovaries of the T1 group were significantly lower than that in control group. However, the levels of KISS1 mRNA in the T2 group were significantly lower than that in the control group only in ovaries (p < 0.05).ConclusionThe oral KISS1-54 DNA vaccine with fused tPA signal peptide was more effective than that KISS1-10 DNA vaccine in suppressing fertility of female rats.     

使用醋酸甲孕酮避孕针对骨质代谢和卵巢功能影响的研究

目的:研究长效醋酸甲孕酮避孕针(DMPA)对生育年龄妇女骨质代谢和卵巢功能影响。方法:选择自愿使用DMPA避孕者30例为实验组,采用避孕套避孕者30例为对照组。①测定两组血清碱性磷酸酶(AKP)、尿钙/肌酐(Ca/cr)、尿羟脯氨酸/肌酐(HYP/Cr);②测定非惯用臂桡尺骨骨密度(BMD)和桡尺骨超远端骨矿含量(BMC);③实验组于用药满一年时,对照组于月经周期第5天采用放免法测定血清性激素值;④实验组于首次用药当日及用药满一年,对照组于月经周期第5天B超监测卵泡发育状况;⑤实验组用药满一年时作阴道脱落细胞检查。结果:两组骨代谢生化指标及桡尺骨骨密度无显著性差异(P>0.05);实验组血清性激素值相当于正常育龄妇女卵泡早期水平,实验组有96.7％研究对象的卵巢内无卵泡或有小卵泡,最大卵泡直径≤1.5cm,卵泡发育状况相当于正常妇女卵泡早期水平,阴道脱落细胞检查显示雌激素水平无低落。结论:使用DMPA一年对骨质代谢无影响;DMPA使用者卵巢功能相当于正常育龄妇女卵泡早期水平。     

Impact of obesity on oral contraceptive pharmacokinetics and hypothalamic-pituitary-ovarian activity

Background

This study was conducted to determine whether increased body mass index (BMI) affects oral contraceptive (OC) pharmacokinetics and suppression of hypothalamic-pituitary-ovarian (HPO) axis activity.

Study Design

Ovulatory reproductive-age women with normal weight (BMI <25 kg/m²; n=10) and with obesity (BMI >30 kg/m²; n=10) received OCs for two cycles (prospective cohort). Subjects were admitted for two 48-h inpatient stays at the beginning and end of the hormone-free interval. Ethinyl estradiol and levonorgestrel (LNG) levels were evaluated during both inpatient stays. Gonadotropin pulsatility (follicle-stimulating hormone and luteinizing hormone) was measured during the second inpatient stay. Estradiol (E₂) and progesterone (P) were measured daily during inpatient stays and twice per week in Cycle 2.

Results

BMI was greater in the obese compared to the normal-BMI group [37.3 kg/m² (SD, 6.0) vs. 21.9 kg/m² (SD, 1.6); p<.05]. The LNG half-life was significantly longer in the obese group (52.1±29.4 vs. 25.6±9.3 h, p<.05), which correlated with a lower maximum LNG concentration on Cycle 2, Day 1 [1.9 ng/mL (SD, 0.5) vs. 2.5 ng/mL (SD, 0.7)] and a longer time to reach steady state (10 vs. 5 days) in obese women. There were no significant differences in volume of distribution between groups. LH pulse parameters did not differ statistically between groups but trended toward greater HPO activity in the obese group. Additionally, more obese (6/10 vs. 3/10 normal BMI, p>.05) women exhibited E₂ levels consistent with development of a dominant follicle and P levels consistent with ovulation (2/10 vs. 1/10) during Cycle 2.

Conclusions

Compared to women with normal BMI, obese women exhibit differences in OC pharmacokinetics that are associated with greater HPO activity.     

芹菜素对雌性大鼠下丘脑-腺垂体-卵巢轴调控作用

目的研究芹菜素(apigenin,Api)对雌性大鼠腺垂体、卵巢颗粒细胞分泌促卵泡激素(follicle stimulating hormone,FSH)、黄体生成素(luteinzing hormone,LH)、雌二醇(estradiol,E2)及孕酮(progesterone,P)的影响。方法应用细胞培养技术,放射免疫测定法及下丘脑-腺垂体-卵巢三级培养细胞顺序灌注法。采用下列顺序灌注法,Api浓度分别为10-4mol/L、10-5mol/L、10-6mol/L,(1)H-AP-O;(2)H-AP(Api)-O;(3)H-AP-O(Api),分别测定腺垂体和卵巢颗粒细胞培养液中FSH、LH、H2及P的含量。结果实验组(3、5、7组)分别与对照组(1组)比较差异有统计学意义(P<0.01),Api(10-4mol/L～10-6mol/L)以浓度依赖方式使培养的雌性动情前期大鼠卵巢颗粒细胞E2及P的含量也呈减少,且随着浓度的增加,E2及P的含量也呈减少趋势;Api组(10-4mol/L～10-6mol/L)动情前期雌性大鼠腺垂体细胞LH、FSH的分泌量与对照组比较差异无统计学意义(P>0.05)。结论 Api...     

预防性护理干预在女性垂体瘤切除术患者围手术期的应用效果

目的探讨预防性护理干预在女性垂体瘤切除术患者围手术期的应用效果。方法选取2019年11月至2020年12月中国科学技术大学附属第一医院南区收治的84例女性垂体瘤切除术患者作为研究对象,根据护理方法的不同分为观察组(42例)和对照组(42例),分别实施预防性护理干预和常规护理,比较两组患者术后并发症发生率、护理满意度及护理前后焦虑自评量表(SAS)和抑郁自评量表(SDS)评分。结果观察组患者术后并发症总发生率低于对照组,差异有统计学意义(P<0.05)。两组护理后的SAS和SDS评分低于护理前,观察组护理后SAS和SDS评分低于对照组,差异有统计学意义(P<0.05)。观察组患者的护理总满意度高于对照组,差异有统计学意义(P<0.05)。结论女性垂体瘤切除术患者实施预防性护理干预,可提高术后并发症的防治效果,促进患者快速、良好康复。