静脉麻醉药抑制利多卡因致大鼠惊厥作用的比较

目的比较静脉麻醉药丙泊酚、依托咪酯、咪达唑仑及硫喷妥钠拮抗利多卡因致大鼠惊厥的作用。方法雄性Wistar大鼠36只,体重(250±20)g,随机均分为六组:空白对照组(C组)、利多卡因组(L组:利多卡因4mg·kg-1·min-1)、利多卡因+丙泊酚组(P组:利多卡因+丙泊酚12.5mg/kg)、利多卡因+依托咪酯组(E组:利多卡因+依托咪酯1.85mg/kg)、利多卡因+咪达唑仑组(M组:利多卡因+咪达唑仑0.65mg/kg)和利多卡因+硫喷妥钠组(T组:利多卡因+硫喷妥钠30.85mg/kg),惊厥后2h处死大鼠,取出脑组织分离双侧海马,一侧用于检测c-fos阳性细胞蛋白的表达。另一侧用于测定一氧化氮(NO)含量及一氧化氮合酶(NOS)活性。结果除C组外,其它五组大鼠均出现了惊厥,给予静脉麻醉药抑制惊厥,五组惊厥持续时间差异无统计学意义。L、P、E、M和T组c-fos阳性细胞表达、NO含量和NOS活性显著高于C组(P<0.05);P、E、M和T组c-fos阳性细胞表达、NO含量及NOS活性均显著降低于L组(P<0.05);M、T组c-fos阳性细胞表达、NO含量及NOS活性显著低于P、E组(P<0.05)。结论静脉麻醉药咪达唑仑、丙泊酚、依托咪酯及硫喷妥钠均可有效抑制利多卡因致惊厥作用,其中咪达唑仑与硫喷妥钠效果更显著。     

铅对大鼠海马C-fos基因表达及学习记忆的影响

目的　观察和探讨铅对大鼠海马C -fos基因表达及学习记忆的影响。方法　选用健康大鼠 30只 ,每天给醋酸铅灌胃 1次 ,高剂量组 0 2 g/ (kg·d) ,低剂量组 0 1g/ (kg·d) ,连续染毒 3个月后 ,用Y型迷宫试验测试大鼠学习记忆能力 ;最后处死大鼠 ,用原位杂交法观察各组大鼠海马C -fosmRNA的表达状况。结果　 ( 1) 2个染铅组大鼠主被动回避反应正确次数显著低于对照组 (P <0 0 1) ;( 2 )光镜下观察高铅组海马切片着色很浅 ,C -fosmRNA阳性细胞很少 ;低铅组着色较浅 ,可见少数C -fosmRNA阳性细胞 ;对照组着色较深 ,C -fos阳性细胞密集 ,阳性锥体细胞呈多角形 ,胞体较大 ,胞浆染色呈不规则的环形。结论　C -fos基因表达水平下降可能是亚慢性铅染毒致大鼠学习记忆障碍的重要环节 ,是铅对学习记忆损害的分子机制之一。     

植物雌激素对去势雌性大鼠缺血性脑损伤的神经保护作用

目的对比研究植物雌激素和动物雌激素对去势雌性SD大鼠永久性局灶性脑缺血组织的神经保护作用。方法采用线栓法建立右侧永久性大脑中动脉阻断模型。缺血24h后立即断头取脑,冠状切片,HE染色后于光镜下观察缺血侧大脑皮层的病理变化,应用免疫组化法检测不同实验组大鼠缺血侧Cfos表达情况,以DNA缺口末端标记法原位检测细胞凋亡,通过TTC染色比较脑梗死体积百分比。结果动物雌激素(17β雌二醇)组及植物雌激素(葛根素)组与生理盐水组相比,光镜下正常神经细胞密度显著增加,缺血侧C-fos表达阳性的细胞数明显减少,凋亡细胞数显著减少,脑梗死体积百分比也明显缩小(P<0.05)。两种雌激素相比,上述4项指标差异均无显著性(P>0.05)。结论两种雌激素对缺血性脑损伤均有保护作用,可减弱大脑缺血梗死灶边缘区的Cfos表达,从而延缓神经细胞凋亡。这可能是雌激素脑保护作用的机制之一。     

c-fos反义寡脱氧核苷酸对茁-淀粉样蛋白31~35神经毒作用的影响

目的研究c-fos基因对茁-淀粉样蛋白31~35神经毒的作用。方法培养原代小鼠皮层神经元,提前加入不同浓度的c-fos反义寡脱氧核苷酸,以DNA电泳分析和流式细胞技术检测其对茁-淀粉样蛋白31~35致凋亡作用的影响。结果低浓度的c-fos反义寡脱氧核苷酸对茁-淀粉样蛋白31-35所引起的神经元凋亡有保护作用。结论c-fos途径是茁-淀粉样蛋白31-35神经毒作用的必需途径。     

Effects of N-Methyl-D-Aspartate (NMDA) on Seasonal Cycles of Reproduction, Body Weight and Pelage Colour in the Male Siberian Hamster

Siberian hamsters (Phodopus sungorus) transferred from stimulatory photoperiods (long days: LD) to inhibitory photoperiods (short days: SD) undergo testicular regression within 8 weeks. This reproductive response to photoperiod was blocked by systemic daily treatment with the glutamatergic agonist N-methyl-D-aspartate (NMDA: 20 mg/kg BW, sc). This powerful effect of NMDA demonstrates the potential for endogenous glutamate to regulate reproductive function. The overall aim of the subsequent studies was to investigate the site and mechanism of action of this glutamatergic agonist in order to identify potential mechanisms through which endogenous glutamate might act. To investigate whether the effect of systemic NMDA was via an effect on the circadian timing system, alterations in gonadal regression and recrudescence, seasonal coat changes (pelage) and body weight (BW) were examined. It would be predicted that long-term cycles of all these seasonal parameters would be affected if the action of NMDA were to perturb the transduction of photoperiodic information. Daily treatments with NMDA, which initially maintained reproductive function in hamsters exposed to SD, did not influence the time course of subsequent testicular recrudescence, nor did they influence long-term cycles of pelage and BW. Moreover, treatment with NMDA induced a dose-dependent increase in serum concentrations of LH within 15 min of systemic injection. These data are consistent with the hypothesis that systemic NMDA exerts it reproductive effects not via an action on the circadian system, but via an action on secretion of GnRH. To investigate potential central sites of action of glutamate, induction of the immediate early gene c-fos, an acute marker of cellular response, was evaluated immunocytochemically (ICC) in brain areas after treatment with NMDA. Although dual-label ICC studies revealed that NMDA did not induce c-fos within GnRH neurons, NMDA did induce c-fos in many cells in the region of the organum vasculosum of the lamina terminalis (OVLT), an area containing a large number of GnRH perikarya, and in the arcuate nucleus, a region close to GnRH secretory terminals in the median eminence. The lack of c-fos induction in GnRH cells argues against a direct effect of NMDA on GnRH neurons. Thus, we examined immunocytochemically the distribution of the common NMDAR1 glutamate receptor subunit to evaluate further the potential sites of glutamatergic action. As expected, NMDAR1-ir was widespread in perikarya throughout the brain, including the region of the OVLT and the arcuate nucleus. However, NMDAR1-ir was also observed in cell processes in hypothalamic areas, including the median eminence, demonstrating the potential for actions of glutamate on neurosecretion in this structure. Collectively, these pharmacological, endocrine and neuroanatomical studies suggest that NMDA acts to release GnRH when delivered systemically, though not necessarily via a direct action on GnRH neurons. These findings are consistent with the view that glutamate is an important regulator of seasonal changes in reproductive function.     

脑缺血再灌注后脑组织C—fos基因表达与丹参的影响

采用线栓法制成大鼠大脑中动脉缺血再灌注模型,用地高辛精标记C-fos探针进行原位杂交。结果示缺血再灌注鼠栓塞侧和丹参组栓塞侧皮层及海马C-fos基因表达显著增多,但丹参组栓塞侧C-fos基因表达显著低于缺血再灌组(P<0.05),而两组栓塞对侧比较无显著差异。表明,脑缺血再灌注后脑组织C-fos基因表达显著增多,丹参能部分抑制缺血后C-fos基因的表达。     

硝普钠控制性降压对兔脑神经元c-fos及细胞凋亡的影响

目的通过观察硝普钠诱导的四种低血压水平对兔脑海马CA1区神经元超微结构、细胞凋亡及c-fos表达的影响,了解脑组织对低血压的耐受性以及探讨安全的降压低限。方法 30只新西兰兔随机均分为五组,MAP分别降至基础值的70%(Ⅰ组)、60%(Ⅱ组)、50%(Ⅲ组)、45%(Ⅳ组)和不降压(Ⅴ组)。目标血压维持1 h,复压2 h处死兔。透射电镜观察海马CA1区神经元超微结构,SP法测定该区c-fos表达,DNA末端标记技术(TUNEL)检测该区细胞凋亡。结果电镜下海马CA1区神经元:Ⅱ组出现细胞肿胀变化,Ⅲ、Ⅳ组出现核固缩及细胞凋亡。c-fos在所有控制性降压组表达增多(P<0.01)。Ⅱ、Ⅲ、Ⅳ组TUNEL荧光强度较Ⅰ、Ⅴ组增强(P<0.01)。结论硝普钠控制性降压可以使海马CA1区神经元出现部分凋亡改变,c-fos能对脑血氧供应变化作出快速反应,且其表达与神经元保护作用有关。     

微囊化异体坐骨神经组织细胞移植对大鼠脊髓损伤后c-fos表达的影响

目的探讨微囊化异体坐骨神经组织细胞移植对大鼠脊髓损伤后c-fos表达的影响。方法95只SD大鼠随机分为4组,A组为微囊化坐骨神经细胞移植组（30只）;B组为坐骨神经细胞移植组（30只）;C组为单纯损伤对照组（30只）,仅用明胶海绵填塞SCI腔隙;D组为正常对照组（5只）,仅打开椎管,暴露脊髓不作移植。用免疫组织化学的方法观察移植术后6h-14d脊髓中c-fos基因的表达情况。结果脊髓半横断损伤后对照组脊髓中6h、12h内表达c-fos阳性的神经元数增多,平均光密度值升高,至24h又明显增强。而A组脊髓后角内的c-fos表达明显低于同时间点的B组和C组（P〈0．05）。结论微囊化坐骨细胞移植可能降低c-fos的表达,并在一定程度上减轻脊髓的继发性损伤。     

先天性巨结肠症C-fos原癌基因表达的研究

目的探讨C-fos原癌基因与先天性巨结肠症发病机制间的关系。方法采用RT-PCR技术及免疫组织化学SP方法对巨结肠无神经节细胞的巨结肠痉挛段以及有神经节细胞的扩张段、正常肠组织各12例标本检测C-fos原癌基因mRNA的表达和观察其蛋白免疫组化状况。结果无神经节细胞的巨结肠痉挛段C-fosmRNA表达水平明显高于有神经节细胞扩张段近端(痉挛段相对含量2．11±0．09,扩张段相对含量0．55±0．06,单位mass),巨结肠扩张段近端与正常肠组织相比无明显差异;C-fos蛋白免疫组化巨结肠无神经节细胞的痉挛段粘膜固有层和粘膜肌层中出现大量的棕褐色C-fos蛋白表达产物,而巨结肠近段的扩张段未见C-fos蛋白表达阳性产物。结论C-fos基因可能参与了神经细胞的损害。C-fosmRNA表达及C-fos蛋白表达异常可能参与先天性巨结肠的发病机制。     

Noradrenergic-induced expression of c-fos in rat cortex: neuronal localization.

β Adrenoceptors in the rat forebrain have been shown to exist predominantly on astrocytes. Studies were undertaken to determine whether the cellular localization of c-fos expression caused by the activation of brain β receptors would have a similar cellular localization. Double label light and electron microscopic immunohistochemical experiments with a glial (glial fibrillary acidic protein, GFAP) and neuronal marker (neurofilament protein, NFP) were undertaken in rats treated with the adrenergic drug, yohimbine. These studies revealed a predominantly neuronal localization of Fos protein in the cerebral cortex. The latter results indicate that neurons are the postsynaptic noradrenergic target cells in which this immediate early gene is expressed in response to the stimulation of β adrenoceptors. The possible relation of these findings to the glial localization of these receptors is discussed.