戊四唑点燃大鼠模型海马结构蛋白激酶C阳性细胞的变化

目的　利用戊四唑点燃大鼠模型 ,研究癫痫大鼠海马结构蛋白激酶C(PKC)阳性细胞的变化。方法　将大鼠分为对照组和模型组 ,模型组大鼠又分为完全点燃组和完全点燃后间歇 2 4h组。用免疫组织化学方法检测了海马和齿状回PKC阳性细胞的变化。结果　PKC阳性细胞主要分布于齿状回的颗粒层 ,在海马的分布主要在分子层 ,数量较少。点燃组大鼠海马和齿状回PKC阳性细胞数量与对照组相比 ,均显著增加 (P <0 0 5 ) ;点燃后间歇 2 4h组与对照组相比 ,无显著性变化 (P >0 0 5 )。结论　PKC阳性细胞表达的增加可能在诱导大鼠点燃中起重要的作用。     

绝经后胰岛素抵抗综合征与雌激素替代治疗

雌激素替代治疗可补充体内雌激素 ,提高绝经期后妇女的胰岛素敏感性 ,使心血管疾病的发病危险性显著降低。雌激素通过间接调节血脂代谢和直接作用于血管组织中的雌激素受体调节血管组织和功能 ,对心血管起保护作用。雌激素 雌激素受体复合物作为反式作用因子调节胰岛素受体、胰岛素受体底物及信号转导效应蛋白和代谢途径关键酶的基因表达 ,改变IR及IRS的磷酸化状态 ,并通过PPAR间接调节其它基因的表达而逆转胰岛素抵抗的损伤     

穹窿下器内雌激素受体阳性细胞的分布

雌激素的生理作用不仅限于促进生殖系统各器官的发育和维持第二性征,还能作用于中枢神经系统,在神经组织的发育、分化,神经功能的维持方面发挥重要作用,并具有一定的神经保护作用.     

雌激素替代抑制萘诱导去卵巢大鼠的晶状体氧化损伤

背景：抗氧化作用可能是雌激素对晶状体保护作用的机制之一,但此机制的具体途径目前仍不明确,同时临床上常用的几种雌激素替代治疗方法对晶状体氧化损伤的影响至今少见报道。 目的：观察雌二醇及其联合孕酮对萘诱导去卵巢雌性大鼠晶状体氧化损伤模型中晶状体混浊情况、晶状体氧化防御系统、脂质过氧化产物及可溶性蛋白水平的影响。 方法：将SD大鼠随机分为假手术组、模型组、雌二醇组、雌二醇+孕酮组,后3组均行双侧卵巢切除。术后2周,4组均用萘混悬液灌胃,定期行裂隙灯显微镜检查观察各组大鼠晶状体变化;灌胃6周后检测晶状体氧化防御系统、脂质过氧化产物及可溶性蛋白水平,测定血清雌二醇和孕酮水平。 结果与结论：与模型组相比,雌二醇组、雌二醇+孕酮组及假手术组晶状体混浊程度轻,出现时间晚,而晶状体超氧化物歧化酶、谷胱甘肽、维生素C,可溶性蛋白含量,血清雌二醇与孕酮水平增高(P  < 0.05或P < 0.01),丙二醛水平降低(P < 0.05)。结果证实,雌二醇及其联合孕酮两种替代治疗方法对萘诱导去卵巢雌性大鼠晶状体的氧化损伤均有抑制作用,其机制与晶状体氧化防御系统的活性、抑制脂质过氧化产物的形成并维持可溶性蛋白的水平有关,抑制晶状体的氧化损伤是雌激素替代治疗发挥晶状体保护作用的机制之一。     

更年期综合征妇女雌激素替代治疗的研究

目的：探讨更年期综合征妇女激素替代治疗相关指标的变化及其临床意义。方法：采用放射免疫分析法、离子电极法及酶法测定了50例更年期综合征患者血清E2、FSH、LH、TC、TG、LDL、HDL、ALP水平及尿Ca/Cr比值。结果：经激素替代治疗，患者改良Kuppormen评分显著下降（P＜0．05，P＜0．01）TC、TG及LDL亦显著下降（P＜0．05），HDL略有上升，但统计差异无显著性（P＞0．05）；E2水平明显升高（P＜0．05），FSH及LH则显著下降（P＜0．05），ALP治疗前后无显著差异（P＞0．05），Ca/Cr比值显著下降（P＜0．05）。结论：研究证实，激素替代治疗更年期综合征有满意疗效。     

左旋18-甲基炔诺酮对大鼠雌激素水平及下丘脑雌激素受体阳性细胞的影响

目的:观察左旋18-甲基炔诺酮(LNG)对大鼠雌激素(E)水平及下丘脑内雌激素受体(ER)阳性细胞的影响。方法:正常雌性SD大鼠分为给药对照组、给药组、停药对照组、停药组,应用免疫组织化学方法显示下丘脑ER阳性细胞并检测血清E浓度。结果:给药组较给药对照组E浓度下降,弓状核(Arc)、下丘脑腹内侧核(VMH)内ER阳性细胞的数量减少、光密度下降。停药后基本恢复正常。结论:长期LNG作用导致给药大鼠血清E水平下降;长期LNG作用引起大鼠下丘脑ER数量减少、活性减低,推测ER可能参与影响促性腺激素释放激素的分泌;停药后ER的形态学变化恢复正常,所以LNG的作用基本上是可逆的。     

激素替代治疗如何取舍

在人的生命得以大大延长的今天,女性中年后由于绝经而带来的心理上的变化日益受到重视。生命是一个整体,整个生命都应该是美丽的,女性不应因年龄和生理上的变化减弱对生活质量的追求。激素替代治疗作为绝经之后的种补充雌激素的手段,其利弊兼而有之。关于这个问题,中外专家有不同的见解。     

心血管系统的雌激素受体

雌激素对心血管系统的保护作用除了对血脂代谢的改善以外 ,主要来自于雌激素对心血管系统的直接作用。雌激素对靶细胞的特异性作用主要通过基因组效应和非基因组效应完成。具有功能活性的雌激素受体广泛存在于心血管系统     

雌激素替代治疗对中年卵巢切除大鼠大脑白质、海马内髓鞘及Lingo-1蛋白的影响

目的检测经短期雌激素替代治疗(ERT)后中年卵巢切除大鼠大脑白质及海马内髓鞘相关指标及Lingo-1的表达,探讨雌激素对髓鞘作用的可能机制。方法 24只中年雌性SD大鼠行双侧卵巢切除术(OVX)后,随机分为安慰剂治疗组(OVX+Veh组)和雌激素替代治疗组(OVX+E组)。ERT 1个月后,Morris水迷宫检测大鼠空间学习和记忆能力;从各组大鼠随机选取10只,透射电子显微镜观察大脑白质及海马内髓鞘的超微结构;Western blot检测大脑白质及海马内髓磷脂碱性蛋白(MBP)及Lingo-1的含量;免疫组化方法检测Lingo-1在大脑白质及海马的分布。结果 OVX+E组大鼠在定位航行实验中的潜伏期显著短于OVX+Veh组大鼠(P0.05);OVX+Veh组大鼠大脑白质和海马存在显著的髓鞘结构变性;OVX+E组大鼠大脑白质和海马中MBP的含量均显著高于OVX+Veh组(P0.05),而OVX+E组大鼠大脑白质和海马中Lingo-1的含量及分布均显著低于OVX+Veh组(P0.05)。结论1个月的ERT对中年卵巢切除大鼠的认知功能及大脑白质和海马内的髓鞘具有明显的保护作用,这种保护作用可能与雌激素下调大脑白质和海马内Lingo-1蛋白的表达有关。     

Raised circulating corticosterone inhibits neuronal differentiation of progenitor cells in the adult hippocampus

Neurons are added throughout life to the dentate gyrus of the hippocampus of the mammalian brain. Progenitors residing in the dentate gyrus progress through three distinct stages of adult neurogenesis: proliferation, survival and differentiation. One of the most potent factors which regulates adult neurogenesis is adrenal-derived glucocorticoids. Raised levels of glucocorticoids suppress progenitor division, while removal of glucocorticoids by adrenalectomy stimulates proliferation of these cells in the dentate gyrus. We have recently reported that both pre- and post-mitotic corticoid environments powerfully regulate survival of progenitor cells in a time-dependent manner. However, it is unknown if glucocorticoids alter the process of neuronal differentiation, since not all of the newly-formed cells acquire a neuronal fate during development. Here we employ triple immuno-fluorescence staining techniques to phenotype surviving progenitor cells 28 days after labeling. Results show that high levels of corticosterone (the major glucocorticoid in rodents) either before or after progenitor labeling discouraged the acquisition of neuronal fate. Similar to its effect on survival, post-mitotic corticosterone also regulates neuronal differentiation in a time-dependent fashion, but this action is most prominent from around 19-27 days after the cells were born. In contrast, a corticoid-free environment either before or after progenitor proliferation did not affect neuronal differentiation. Combining these data with previous survival data obtained from the same animals allowed us to estimate the total number of neurons formed resulting from different corticoid treatments. Raised corticosterone significantly reduced neuronal production while adrenalectomy resulted in significantly higher number of neurons in the adult male rat hippocampus.     

Repeated estradiol administration alters different aspects of neurogenesis and cell death in the hippocampus of female, but not male, rats

Estradiol has been shown to have neuroprotective effects, and acute estradiol treatment enhances hippocampal neurogenesis in the female brain. However, little is known about the effects of repeated administration of estradiol on the female brain, or about the effects of estradiol on the male brain. Gonadectomized male and female adult rats were injected with 5-bromo-2-deoxyuridine (BrdU) (200 mg/kg), and then 24 h later were given subcutaneous injections of either estradiol benzoate (33 mug/kg) or vehicle daily for 15 days. On day 16, animals were perfused and the brains processed to examine cells expressing Ki-67 (cell proliferation), BrdU (cell survival), doublecortin (young neuron production), pyknotic morphology (cell death), activated caspase-3 (apoptosis), and Fluoro-Jade B (degenerating neurons) in the dentate gyrus. In female rats, repeated administration of estradiol decreased the survival of new neurons (independent of any effects on initial cell proliferation), slightly increased cell proliferation, and decreased overall cell death in the dentate gyrus. In male rats, repeated administration of estradiol had no significant effect on neurogenesis or cell death. We therefore demonstrate a clear sex difference in the response to estradiol of hippocampal neurogenesis and apoptosis in adult rats, with adult females being more responsive to the effects of estradiol than males.     

复方丹参对脑缺血再灌注后大鼠海马和齿状回神经细胞凋亡及Bcl-2 mRNA表达的影响

目的:探讨中药复方丹参对大鼠脑缺血再灌注后海马和齿状回神经细胞凋亡及Bcl-2 mRNA表达的影响。方法:采用大脑中动脉内栓线法建立大鼠大脑中动脉缺血再灌注模型,应用原位细胞凋亡检测和原位杂交技术检测大鼠海马和齿状回神经细胞凋亡和Bcl-2 mRNA的表达并做图像分析。结果:与假手术对照组比较,缺血再灌注组凋亡神经细胞主要位于缺血侧海马CA1、CA3区,齿状回凋亡细胞较少。3个区神经细胞Bcl-2mRNA的表达在缺血再灌注2 h后升高,随时间的延长逐渐增强。复方丹参组神经细胞Bcl-2 mRNA的表达明显强于缺血再灌组,而凋亡神经细胞数明显较低。结论:复方丹参可通过上调神经细胞Bcl-2 mRNA的表达,抑制神经细胞凋亡,从而减轻缺血再灌注对大鼠海马和齿状回的损伤。     

植物雌激素对去卵巢大鼠海马NOS阳性神经元及学习记忆的影响

目的 :观察植物雌激素对去卵巢大鼠海马NOS阳性神经元及学习、记忆的影响 ,对中枢神经系统的保护作用。方法 :采用NADPH d酶组化观测各组大鼠海马各功能亚区NOS阳性神经元数目和Morris水迷宫行为学方法。结果 :定位航行实验显示各组大鼠的平均逃避潜伏期无明显差异 ,而空间探索实验显示植物雌激素组平台象限的游泳距离百分比和穿台次数均高于去卵巢对照组。在海马CA1和齿状回 (DG) ,植物雌激素组NOS阳性神经元数目较去卵巢对照组明显增多 (P <0 .0 5 )。结论 :植物雌激素能增加海马神经元NOS的表达 ,改善去卵巢大鼠的学习记忆能力 ,提示对中枢神经系统退行性病变具有保护作用。     

胰岛素对糖尿病大鼠海马一氧化氮合酶阳性神经元变化的影响

观察实验性糖尿病大鼠海马一氧化氮合酶（NOS）阳性神经元变化及胰岛的治疗作用。给成年SD大鼠腹腔注射链脲佐菌素制备糖尿病大鼠模型，每日给予长效胰岛素2－3U使血糖低于10mmol/L，于第3月及第6月末以NADPH－d组化法显示海马NOS阳性神经元。并做Morris水迷宫行为学测试。海马NOS阳性神经元密度变化如下：糖尿病组齿状回3月时显著减少（P＜0．01），6月时更明显（P＜0．01）；CA1区6月时显著降低（P＜0．01）；治疗组齿状回3月时恢复正常，而6月时低于正常（P＜0．01）但高于糖尿病组3月时（P＜0．05），CA1区3月，6月均恢复正常。行为学测试中各组大鼠逃避潜伏期变化与齿状回NOS阳性神经元密度变化一致。以上变化可能与糖尿病学习记忆功能损伤有关。胰岛素治疗可延缓其发生。     

Differential modulation of unapposed connexin 43 hemichannel electrical conductance by protein kinase C isoforms

Opening of unapposed connexin 43 hemichannels (Cx43Hc) in the plasma membrane results in altered ionic homeostasis leading to cell damage. Although it is generally acknowledged that Cx43Hc function is regulated by protein kinase C (PKC), information regarding the functional role of PKC in the modulation of Cx43Hc electrical conductance is lacking. In this work, we used the patch-clamp technique to study the effect of phorbol 12-myristate 13-acetate (PMA), a general PKC activator, on the electrical conductance of exogenous Cx43Hc expressed in tsA201 cells. Subsequently, a matrix of synthetic PKC isoform-specific inhibitor peptides was used to dissect the functional role of individual PKC isoforms in Cx43Hc regulation. Superfusion with 10 nM PMA abolished Cx43Hc currents by 74%, an effect that was prevented by pretreatment with a general PKC inhibitor, GF109203X. It is interesting to note that intracellular diffusion of ɛV_1–2 (0.1 μM), an ɛPKC-specific inhibitor peptide, completely antagonized PMA-induced current inhibition. Cell dialysis with either β_II- or δPKC inhibitor peptides partially decreased PMA effect. Neither α- nor β_IPKC inhibition altered PMA-induced current reduction. This study shows for the first time that Cx43Hc electrical conductance is inhibited after PKC activation. Moreover, this inhibition is predominantly mediated by the “novel” ɛPKC isoform, whereas partial inhibition may be provided by the “conventional” β_IIPKC as well as the “novel” δPKC isoforms.     

孕鼠铝暴露对仔鼠齿状回神经干细胞的影响

目的:探讨孕鼠铝暴露对其仔鼠海马齿状回神经干细胞的影响.方法:雌性SD大鼠在围产期经灌胃染铝(对照组以蒸馏水、染铝组以AlCl3 100mg·kg-1·d-1灌胃),分别取胚胎18d、1月、3月龄仔代鼠脑组织,常规石蜡包埋,冠状连续切片,对海马齿状回经巢蛋白免疫组织化学显色,对阳性反应细胞进行计数,测量阳性反应产物的平均光密度.结果:染铝组子代巢蛋白免疫组织化学显色阳性细胞数均明显少于对照组,阳性反应产物平均光密度值低于对照组.结论:大鼠孕期染铝可抑制子代鼠齿状回颗粒层神经干细胞增殖,铝可能抑制海马神经发生.