二甲双胍对大鼠垂体—性腺轴内分泌功能的影响

目的研究二甲双胍(Metformin,MF)对大鼠垂体-性腺轴内分泌功能的影响。方法采用放射免疫分析法和电子显微镜技术,系统研究MF对大鼠血清性激素含量及靶腺组织形态的影响。结果MF135mg·kg-1·d-1,ig,连续用药14d,可使♂大鼠睾酮(T)的含量及♀大鼠血清黄体生成素(LH)水平明显降低,而对♀大鼠卵泡刺激素(FSH)、雌二醇(E2)、孕酮(P)的含量和♂大鼠血清LH、FSH的含量均无影响。270mg·kg-1·d-1MF除明显降低♂大鼠血清T和♀大鼠血清LH的含量外,可使♀大鼠血清P、E2的含量升高(P<0.01)。电镜观察显示,大鼠睾丸内分泌细胞超微结构发生退行性改变,而卵巢细胞超微结构则呈现分泌旺盛的表现。结论MF对♀大鼠垂体-卵巢轴内分泌功能有促进作用,而对♂大鼠垂体-睾丸轴内分泌功能有抑制作用,且使靶腺内分泌细胞的超微结构出现相应的变化。     

甲状腺素对大鼠胰岛β细胞作用和机制的研究

目的研究甲状腺素对大鼠胰岛β细胞功能的影响及其机制。方法采用放射免疫测定法和电镜技术,观察甲状腺素对大鼠血清葡萄糖、胰岛素、肿瘤坏死因子(TNF)、白介素-1β(IL-1β)水平的影响和胰岛β细胞超微结构的改变。结果甲状腺素600μg·kg^-1·d^-1,灌胃(ig),连续14 d,大鼠血清胰岛素水平明显降低,而血糖含量、IL-1β水平则显著升高,同时电镜发现大鼠胰岛β细胞的超微结构呈现退行性改变。结论甲状腺素大剂量长期应用对大鼠胰岛β细胞内分泌功能有抑制作用,其机制与细胞因子IL-1β分泌增多,诱导胰岛β细胞凋亡有关。     

甲状腺素对大鼠胰岛β细胞作用和机制的研究

目的研究甲状腺素对大鼠胰岛β细胞功能的影响及其机制。方法采用放射免疫测定法和电镜技术,观察甲状腺素对大鼠血清葡萄糖、胰岛素、肿瘤坏死因子(TNF)、白介素-1β(IL-1β)水平的影响和胰岛β细胞超微结构的改变。结果甲状腺素600μg.kg-1.d-1,灌胃(ig),连续14 d,大鼠血清胰岛素水平明显降低,而血糖含量、IL-1β水平则显著升高,同时电镜发现大鼠胰岛β细胞的超微结构呈现退行性改变。结论甲状腺素大剂量长期应用对大鼠胰岛β细胞内分泌功能有抑制作用,其机制与细胞因子IL-1β分泌增多,诱导胰岛β细胞凋亡有关。     

胃癌伴神经内分泌分化和胃混合性腺神经内分泌癌临床病理及预后分析

　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　【摘要】目的 探讨胃癌伴神经内分泌分化和胃混合性腺神经内分泌癌的临床病理及预后。方法 回顾性分析61例胃癌伴神经内分泌分化和34例胃混合性腺神经内分泌癌患者的临床病理资料,对其组织化学及免疫组织化学染色进行观察。结果 胃癌伴神经内分泌分化和胃混合性腺神经内分泌癌患者肿瘤发病部位、远处转移及区域淋巴结转移差异有统计学意义（P<0.05）;SyN 、CgA和CD56三者阳性表达率差异有统计学意义（P<0.05）;区域淋巴结转移和远处转移2个因素与预后相关（P<0.05）;胃混合性腺神经内分泌癌患者术后生存期短于胃癌伴神经内分泌分化患者（P<0.05）。结论 免疫组化染色对胃癌伴神经内分泌分化和胃混合性腺神经内分泌癌的确诊具有重要意义,肿瘤神经内分泌细胞数量的多少对患者预后评估及辅助治疗有指导意义。      

左旋甲状腺素对心血管的作用

甲状腺机能亢进(甲亢)病人,时常并发心血管系统疾病。许多学者都曾以外源性甲状腺素(T_4)或三碘甲状腺原氨酸(T_3)处理动物,作为甲亢动物模型进行实验,据文献报道,甲状腺机能亢进动物心肌的肾上腺素受体数目有所改变。本文给家兔注射大剂量左旋甲状腺素,观察其对心脏、血压、     

胸腺因子D对老龄大鼠垂体-性腺轴内分泌激素的影响

目的　探讨胸腺因子 D对垂体 -性腺轴内分泌衰老的延缓作用。 方法 　雌、雄 2 1月老龄 SD大鼠各随机分成两组 ,一组隔日背部皮下注射胸腺因子 D2 mg· kg- 1 ,另一组及 6月青龄雌、雄对照注射等量生理盐水 ,连续处理 3个月后 ,用放射免疫法测定腺垂体组织、血清 FSF、L H和血清 E2 、T。结果 　与雄性青龄对照组相比 ,雄性老年血清 L H升高 ,血清 T和 E2 下降 ,给药后 ,这些老年性改变可部分得到改善 ,而腺垂体组织FSH和血清 FSH、L H、E2 、T在各雌性大鼠间无差异。结论 　胸腺因子 D可逆转老龄雄性大鼠垂体 -性腺轴内分泌激素的老龄性改变 ,从而延缓衰老     

克罗米芬联合人绝经期促性腺激素治疗内分泌失调性不孕症及对患者血清泌乳素的影响

目的：探讨克罗米芬（枸橼酸氯米芬胶囊,CC）联合人绝经期促性腺激素（ HMG）治疗内分泌失调性不孕症的临床效果并分析其对血清泌乳素的影响。方法将200例内分泌失调性不孕症患者随机分为试验组和对照组各100例。在对不孕症患者进行常规治疗和护理的基础上,试验组采用CC联合HMG进行不孕治疗,对照组采用传统不孕症的治疗措施,2个月后比较2组患者治疗期间排卵数量和妊娠情况,以及治疗前后患者血清泌乳素水平变化。结果试验组患者治疗期间排卵率和最终妊娠率均高于对照组,差异均有统计学意义（ P＜0．05）。2组患者治疗后均有不同程度下降,且试验组下降幅度大于对照组,差异均有统计学意义（ P＜0．05）。结论 CC联合HMG对内分泌失调性不孕症患者的治疗效果显著,并可降低患者血清泌乳素水平。     

电镜观察甲状腺素对大鼠垂体-卵巢轴的作用

目的:观察甲状腺素(thyroxine,T4)对大鼠垂体、卵巢超微结构的影响。方法:用透射电子显微镜观察经甲状腺素0.6μg.g-1.d-1,ig,21d后大鼠垂体、卵巢细胞超微结构的改变。结果:实验组大鼠垂体促性腺激素细胞的核膜不清晰,部分核膜消失,线粒体脊断裂或消失,出现髓样变和空泡变;粗面内质网有肿胀,出现部分脱颗粒现象。实验组大鼠卵巢内分泌细胞中,部分细胞之间出现间隙,颗粒细胞线粒体出现髓样变和空泡变,高尔基体、核糖体减少,可见髓样小体。结论:长期大剂量应用甲状腺素引起大鼠腺垂体、卵巢内分泌细胞超微结构产生退行性改变。     

银杏叶提取物对甲状腺素致大鼠心肌肥厚的保护作用

目的：探讨银杏叶提取物对大鼠心肌肥厚的保护作用及其相关作用机制。方法将21只SD大鼠随机分为银杏叶提取物组、模型组和对照组各7例,银杏叶提取物组和模型组采用L-甲状腺素皮下注射建立大鼠心肌肥厚模型。银杏叶提取物组给予银杏叶提取物灌胃,其他2组给予同体积生理盐水灌胃,连续14d,取心脏称重后全心重量指数（ HWI）及左心重量指数（ LVMI）;分别检测心肌组织一氧化氮合酶（ NOS）活性、心肌组织血管紧张素Ⅱ（ AngⅡ）及钙调神经磷酸酶（ CaN）的水平。结果与模型组相比,银杏叶提取物能显著改善HWI和LVMI,心肌组织NOS活性显著升高,AngⅡ含量降低,CaN活性明显降低。结论银杏叶提取物对甲状腺腺素所致大鼠心肌肥厚具有保护作用,其作用机制与提高NOS水平、降低CaN活性、抑制AngⅡ有关。     

重型肝炎甲状腺素检测及血浆置换对甲状腺素水平的影响

重型肝炎肝细胞大量坏死,肝功能衰竭,合成及代谢能力下降,从而影响血清甲状腺素水平。血浆置换是目前治疗重型肝炎的有效措施之一,它不仅能清除体内的有毒代谢产物,而且能够部分补充人体所需的蛋白、凝血因子等物质。笔者检测了重型肝炎患者血清甲状腺素水平变化,并观察了血浆置换对甲状腺素水平的影响,报告如下。     

Effect of SMP-028 on steroidogenesis in rats; mechanism of toxicological events on endocrine organs of rats

SMP-028 is a new compound for treatment of asthma. Oral administration of SMP-028 to rats was associated with toxicological events in endocrine organs. These events mainly consisted of pathological changes in the adrenal gland, testis, prostate, seminal vesicle, ovaries, and uterus. In this study, we set to clarify whether SMP-028 inhibits steroidogenesis in primary culture cells obtained from rat endocrine organs in vitro. Adrenal cells, testicular cells, and ovarian cells were treated with SMP-028 and the production of steroid hormones, i.e., progesterone, aldosterone, corticosterone, total testosterone, and estradiol from these cells was measured by radioimmunoassay. We found that the production of progesterone from these cells treated with SMP-028 at 1 μM decreased to 16–67% that of the control. These findings indicate that SMP-028 inhibits steroidogenesis in rat endocrine organs in vitro. Considering that free maximum concentration in rats treated with SMP-028 are higher than the IC₅₀ values for the inhibition of steroidogenesis in vitro, it is therefore believed that the toxicological events seen in rats following treatment with SMP-028 are due to inhibition of steroidogenesis in vivo.     

Biosensor discovery of thyroxine transport disrupting chemicals

Ubiquitous chemicals may interfere with the thyroid system that is essential in the development and physiology of vertebrates. We applied a surface plasmon resonance (SPR) biosensor-based screening method for the fast screening of chemicals with thyroxine (T4) transport disrupting activity. Two inhibition assays using the main thyroid hormone transport proteins, T4 binding globulin (TBG) and transthyretin (TTR), in combination with a T4-coated biosensor chip were optimized and automated for screening chemical libraries. The transport protein-based biosensor assays were rapid, high throughput and bioeffect-related. A library of 62 chemicals including the natural hormones, polychlorinated biphenyls (PCBs), polybrominated diphenylethers (PBDEs) and metabolites, halogenated bisphenol A (BPA), halogenated phenols, pharmaceuticals, pesticides and other potential environmentally relevant chemicals was tested with the two assays. We discovered ten new active compounds with moderate to high affinity for TBG with the TBG assay. Strikingly, the most potent binding was observed with hydroxylated metabolites of the brominated diphenyl ethers (BDEs) BDE 47, BDE 49 and BDE 99, that are commonly found in human plasma. The TTR assay confirmed the activity of previously identified hydroxylated metabolites of PCBs and PBDEs, halogenated BPA and genistein. These results show that the hydroxylated metabolites of the ubiquitous PBDEs not only target the T4 transport at the TTR level, but also, and to a great extent, at the TBG level where most of the T4 in humans is circulating. The optimized SPR biosensor-based transport protein assay is a suitable method for high throughput screening of large libraries for potential thyroid hormone disrupting compounds.     

艾滋病患者血清甲状腺激素变化及其临床意义

目的检测艾滋病（AIDS）患者血清甲状腺激素含量,观察其含量变化及临床意义。方法采用化学发光法测定AIDS患者血清总三碘甲腺原氨酸（T3）、总甲状腺素（T4）、游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺激素（TSH）含量并作统计分析。结果艾滋病患者血清T3、FT3含量明显低于健康对照组[（1．78±0．99）与（2．43±0．52）nmol／L,（3．75±3．65）与（5．68±1．83）pmol／L,均P〈0．05];T4、FT4、TSH与健康对照组差异无统计学意义（均P〉0．05）。结论血清甲状腺激素含量变化对反映艾滋病患者病情有重要临床意义。     

Effects of environmental endocrine disruptors,including insecticides used for malaria vector control on reproductive parameters of male rats

The male reproductive system is sensitive to endocrine disrupting chemicals (EDCs) during critical developmental windows. Male Sprague-Dawley rats were exposed in utero-, during lactation- and directly to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), 1,1,-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and a mixture of DDT, deltamethrin (DM), p-nonylphenol (p-NP) and phytoestrogens, at concentrations found in a malaria-area. After dosing for 104 days, histological assessments and reproductive-endpoints were assessed. The anogenital distance (AGD) (P = 0.005) was shorter in the mixture-exposed group, while the prostate mass (P = 0.018) was higher in the DDT-exposed group. A higher testicular mass and abnormal histology was observed in the DDT-(P = 0.019), DDE-(P = 0.047) and mixture-exposed (P < 0.005) groups. This study shows that in utero-, lactational- and direct exposure to EDCs present in a malaria-area negatively affects male reproductive parameters in rats. These findings raise concerns to EDC-exposures to mothers living in malaria-areas and the reproductive health of their male offspring.     

Effects of endocrine disruptors on arachidonic acid metabolism in rabbit platelets

To explore the possible actions of endocrine disruptors on the autacoid synthesis in the body, we investigated the effects of nonylphenol (NP), bisphenol A (BPA), di-n-butyl phthalate (DBP), benzyl-n-butyl phthalate (BBP), and di-2-ethylhexyl phthalate (DEHP) on the formation of 12-lipoxygenase metabolite, 12-HETE, and cyclooxygenase metabolites, TXB(2) and 12-HHT, from exogenous arachidonic acid (AA) in rabbit platelets. NP (10-50 microM) showed strong inhibition on the formation of cyclooxygenase metabolites (TXB(2), 34-95% inhibition; 12-HHT, 13-78% inhibition) and weaker inhibition on the formation of 12-HETE (0-49% inhibition). BPA, DBP, BBP, DEHP, and 17beta-estradiol (endogenous estrogen) failed to show any effect on the formation of cyclooxygenase and 12-lipoxygenase metabolites at concentrations up to 100 microM. These results suggest that NP inhibits AA metabolism in platelets and that its effects on the cyclooxygenase pathway predominate over those exerted via the 12-lipoxygenase pathway.     

Risk assessment of ‘endocrine substances’: Guidance on identifying endocrine disruptors

The European regulation on plant protection products (1107/2009) and other related legislation only support the marketing and use of chemical products on the basis that they do not induce endocrine disruption in humans or wildlife species. This legislation would appear to make the assumption that endocrine active chemicals should be managed differently from other chemicals presumably due to an assumed lack of a threshold for adverse effects. In the absence of agreed scientific criteria and guidance on how to identify and evaluate endocrine activity and disruption within these pieces of legislation, a European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) task force was formed to provide scientific criteria that may be used within the context of these three legislative documents. The first ECETOC technical report and associated workshop, held in 2009, presented a science-based concept on how to identify endocrine activity and disrupting properties of chemicals for both human health and the environment. Specific scientific criteria for the determination of endocrine activity and disrupting properties that integrate information from both regulatory toxicity studies and mechanistic/screening studies were proposed. These criteria combined the nature of the adverse effects detected in studies which give concern for endocrine toxicity with an understanding of the mode of action of toxicity so that adverse effects can be explained scientifically. A key element in the data evaluation is the consideration of all available information in a weight-of-evidence approach.     

Differential regulation of thyroid hormone receptor-mediated function by endocrine disruptors

It is well known that endocrine disruptors (EDs) act as anti-estrogenic agents and affect the function of reproductive organ. EDs are also thought to affect thyroid hormone (TH) system which is important for biological functions such as growth, development and metabolism. However, it is still not clear how EDs are able to regulate TH receptor (TR)-mediated functions. In this study, therefore, the modulatory effects of representative EDs such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyl (Aroclor 1254) and bisphenol A (BPA) were examined using TR-expressing GH3 cells (a rat pituitary gland epithelial tumor cell line) activated by triiodothyronine (T3). EDs tested significantly blocked T3 binding to TR in a dose-dependent manner. Biochemical characterization by Scatchard and Lineweaver-Burk plot analyses indicated that TCDD and aroclor 1254 bound to TH receptors in a competitive inhibitory manner, whereas BPA bound to TH receptors in a non-competitive pattern. The different inhibitory mode of action by EDs was also found in regulating TR-mediated production of prolactin (PRL). Aroclor 1254 exposure for 48 h enhanced T3-mediated PRL production, but BPA down-regulated. These results suggest that the EDs (TCDD, Aroclor 1254 and BPA) could differentially bind to TR and distinctly regulate the action of TR function, even though EDs are structurally similar.     

Influence of repeated cocaine exposure on the endocrine and behavioral responses to stress in rats

Previous studies have determined that chronic cocaine exposure inhibits the serotonergic stimulation of hormone secretion. The present experiments were conducted to determine whether the endocrine responses to stress could be a useful approach to assess the influence of cocaine exposure on neuronal function. Male rats received twice daily injections of cocaine (1–15 mg/kg, IP) for 7 days. Animals were subsequently exposed to different stressors, i.e. conditioned emotional stress utilizing a low (0.5 mA) or high (1.5 mA) intensity footshock during training, or to immobilization stress. Immediately after the stress procedures, blood samples were collected for radioimmunoassay of plasma corticosterone, prolactin, and renin concentrations. Repeated cocaine exposure attenuated the stress-induced elevations of corticosterone and prolactin secretion, and attenuated some of the behavioral effects of the low intensity conditioned emotional stress. When exposed to the high intensity conditioned emotional stress, cocaine did not alter the endocrine or behavioral effects of stress. Finally, repeated cocaine exposure modified the immobilization stress-induced elevation of renin secretion; low doses of cocaine (1 or 5 mg/kg) attenuated, while higher doses (10 mg/kg) potentiated the renin response to immobilization stress. Thus, the influence of repeated cocaine exposure on the endocrine and behavioral responses to stress appears to depend upon the type and intensity of the stressor. Compared with previous studies which found altered neuroendocrine responses to serotonin releasers and agonists following cocaine exposure, the hormonal responses to stress are less consistently modified by cocaine.     

齐拉西酮与奥氮平对女性精神分裂症患者阴性和阳性症状与内分泌代谢的影响研究

目的观察齐拉西酮与奥氮平对女性精神分裂症(SCZ)患者阴性和阳性症状与内分泌代谢的影响。方法70例女性SCZ患者,按治疗方法不同分为甲组和乙组,各35例。甲组采用齐拉西酮治疗,乙组采用奥氮平治疗。统计比较两组患者不良反应发生情况及治疗前后阴性和阳性症状评分、空腹血糖(FBG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(HDH-C)、胰岛素抵抗指数(HOMA-IR)。结果治疗前,甲组阴性、阳性症状评分分别为(22.4±5.0)、(16.8±3.5)分,乙组阴性、阳性症状评分分别为(21.9±4.7)、(16.6±3.6)分;治疗3个月后,甲组阴性、阳性症状评分分别为(18.5±4.0)、(13.4±2.8)分,乙组阴性、阳性症状评分分别为(17.9±4.2)分、(13.2±2.9)分;治疗后,两组阴性、阳性症状评分均低于本组治疗前,差异有统计学意义(P<0.05);治疗前及治疗后,两组阴性、阳性症状评分组间比较差异无统计学意义(P>0.05)。甲组治疗前后FBG、HOMA-IR、TC、TG、HDL-C、LDL-C水平比较差异无统计学意义(P>0.05);乙组治疗前后HDL-C水平比较差异无统计学意义(P>0.05);乙组治疗后FBG、HOMA-IR、TC、TG、LDL-C水平均高于本组治疗前及甲组,差异有统计学意义(P<0.05);乙组治疗后HDL-C水平与甲组比较差异无统计学意义(P>0.05)。甲组胃肠道反应、体质量增加发生率均低于乙组,差异有统计学意义(P<0.05);两组嗜睡、头痛发生率比较差异无统计学意义(P>0.05)。结论齐拉西酮与奥氮平治疗女性SCZ均能较好的改善患者的临床症状,但齐拉西酮对机体内分泌代谢指标的影响更小,用药安全性较高,更具有推广价值。