白细胞介素—1和阿片肽促进大鼠大脑皮层神经细…

对白细胞介素－１（ＩＬ－１）、脑啡肽、β－内啡肽及即刻早期基因ｃ－ｆｏｓ、ｃ－ｊｕｎ与癫痫发病机理的研究。结果显示ＩＬ－１、ＩＬ－１受体拮抗剂、β－内啡肽、抗β－内啡肽抗血清、亮－脑啡肽（ＬＥ）均能促进大脑皮层神经细胞ｃ－ｆｏｓ、ｃ－ｊｕｎ ｍＲＮＡ表达，但ＩＬ－１受体拮抗剂、抗β－内啡肽抗血清促ｃ－ｆｏｓ、ｃ－ｊｕｎ ｍＲＮＡ表达量明显低于ＩＬ－１、ＬＥ及β－内啡肽的作用，并能部分抑制后者的作用     

白细胞介素－1和阿片肽促进大鼠大脑皮层神经细胞c－fos及c－jun mRNA表达

对白细胞介素－１（ＩＬ－１）、脑啡肽、β－内啡肽及即刻早期基因ｃ－ｆｏｓ、ｃ－ｊｕｎ与癫痫发病机理的研究。结果显示ＩＬ－１、ＩＬ－１受体拮抗剂、β－内啡肽、抗β－内啡肽抗血清、亮－脑啡肽（ＬＥ）均能促进大脑皮层神经细胞ｃ－ｆｏｓ、ｃ－ｊｕｎｍＲＮＡ表达，但ＩＬ－１受体拮抗剂、抗β－内啡肽抗血清促ｃ－ｆｏｓ、ｃ－ｊｕｎｍＲＮＡ表达量明显低于ＩＬ－１、ＬＥ及β－内啡肽的作用，并能部分抑制后者的作用；ＩＬ－１、β－内啡肽、ＬＥ促ｃ－ｆｏｓｍＲＮＡ表达在一定范围呈现量效关系；ＩＬ－１诱导ｃ－ｆｏｓ、ｃ－ｊｕｎｍＲＮＡ表达呈现时间效应关系，均为短暂表达。由于具有不同生物学效应的因子均能诱导不同程度ｃ－ｆｏｓ、ｃ－ｊｕｎｍＲＮＡ表达，提示它们对靶基因的调控具有正性及负性双向性，对神经细胞兴奋性产生不同作用。     

吗啡依赖与戒断大鼠伏隔核单胺,类阿片肽及下丘脑POMC mRNA改变…

研究了大鼠吗啡依赖与戒断状态和伏隔核类阿片肽、单胺、下丘脑ＰＯＭＣ基因表达改变之间的关系。发现在吗啡依赖状态伏隔核内β－内啡肽、脑啡肽、单胺释放以及下丘脑ＰＯＭＣ基因表达受抑制。戒断４８小时后强啡肽、ＮＥ、ＭＨＰＧ、５－ＨＴ升达高峰，后虽水平有所降低，但戒断１周时仍高于对照显著。深受抑制的ＤＡ、β－内啡肽释放以及ＰＯＭＣ基因表达在戒断后有所回升，但于戒断１周时还是显著低于对照水平。提出这些生化改变     

吗啡依赖与戒断大鼠伏隔核单胺、类阿片肽及下丘脑POMCmRNA改变的研究

研究了大鼠吗啡依赖与戒断状态和伏隔核类阿片肽、单胺、下丘脑ＰＯＭＣ基因表达改变之间的关系。发现在吗啡依赖状态伏隔核内β－内啡肽、脑啡肽、单胺释放以及下丘脑ＰＯＭＣ基因表达受抑制。戒断４８小时后强啡肽、ＮＥ、ＭＨＰＧ、５－ＨＴ升达高峰，后虽水平有所降低，但戒断１周时仍高于对照显著。深受抑制的ＤＡ、β－内啡肽释放以及ＰＯＭＣ基因表达在戒断后有所回升，但于戒断１周时还是显著低于对照水平。提出这些生化改变尤其是自从依赖形成后ＤＡ的持续低水平是吗啡依赖的机理之一。     

肺癌患者红细胞CR1基因密度型分布与红细胞免疫变？…

目的 检测３２例肺癌患者红细胞ＣＲ１基因密度型分布，红细胞免疫粘附肿瘤细胞功能及ＳＯＤ酶活性、β－内啡肽含量。方法 ＰＣＲ法检测红细胞ＣＲ１基因密度多态性，红细胞花环法检测红细胞免疫粘附肿瘤细胞能力；放免法测定ＳＯＤ酶活性；ＲＩＡ法测定β－内啡肽含量。     

白细胞介素—1与阿片肽在大鼠大脑皮层细胞中的相互作用

白细胞介素－１（ＩＬ－１）及阿片肽作为免疫与神经系统之间调节的介质与中枢神经系统生理及病理生理的变化密切相关，我们探讨了ＩＬ－１和阿片肽在培养在大鼠脑皮层神经细胞中的相互作用。结果表明，ＩＬ－１β明显促进大脑皮层细胞前脑啡肽原ｍＲＮＡ表达及亮脑啡肽分泌增加，对β－内啡肽分泌有一定影响，ＩＬ－１受体拮抗剂能抑制ＩＬ－１的作用，亮脑啡肽不能促进大脑皮层神经细胞ＩＬ－１βｍＲＮＡ表达及ＩＬ－１活性改变。     

药物对吸烟者血浆β-内啡肽与皮质醇水平的影响

观察药物对吸烟者血浆β－内啡肽和皮质醇水平的变化,探讨它们之间的相互关系,应用放射免疫分析法进行检测,吸烟组的血浆皮质醇及β－内啡肽明显高于对照组;自然戒断烟后,戒烟组的血浆皮质醇明显升高,而血浆β－内啡肽明显降低;治疗后,吸烟组的血浆β－内啡肽和皮质醇达到平衡,用药物戒烟可能是通过改善内源性阿片肽及下丘脑－垂体－肾上腺轴的功能而达到戒烟的效果。     

白细胞介素－1与阿片肽在大鼠大脑皮层细胞中的相互作用

白细胞介素－１（ＩＬ－１）及阿片肽作为免疫与神经系统之间调节的介质与中枢神经系统生理及病理生理的变化密切相关。我们探讨了ＩＬ－１和阿片肽在培养的大鼠脑皮层神经细胞中的相互作用。结果表明，ＩＬ－１β明显促进大脑皮层细胞前脑啡肽原ｍＲＮＡ表达及亮脑啡肽分泌增加；对β－内啡肽分泌有一定影响；ＩＬ－１受体拮抗剂能抑制ＩＬ－１的作用；亮脑啡肽不能促进大脑皮层神经细胞ＩＬ－１βｍＲＮＡ表达及ＩＬ－１活性改变。提示在大脑皮层神经细胞中，ＩＬ－１和阿片肽间仅存在单向作用，ＩＬ－１对中枢神经系统的部分作用可能依赖于阿片肽的神经调节作用。     

β—内啡肽在先兆流产孕妇中变化的初步观察

观察并分析β-内啡肽在先兆流产孕妇中的变化，初步探讨β－内啡肽在怀孕中的作用，方法：病例组和对照组各30例病例采用放射免疫方法进行血清β-内啡肽测定，结果：对照组B组，对照组A组，病例组均有显著差异性，结论：β－内啡肽在先兆流产孕妇中具有类似细胞因子的免疫功能，对维持正常妊娠具有一定的作用。     

肺癌患者红细胞CR1基因密度型分布与红细胞免疫变化的研究

目的检测３２例肺癌患者红细胞ＣＲ１基因密度型分布、红细胞免疫粘附肿瘤细胞功能及ＳＯＤ酶活性、β－内啡肽含量。方法ＰＣＲ法检测红细胞ＣＲ１基因密度多态性；红细胞花环法检测红细胞免疫粘附肿瘤细胞能力；放免法测定ＳＯＤ酶活性；ＲＩＡ法测定β－内啡肽含量。结果经与３１例正常人比较显示：肺癌患者ＣＲ１基因密度多态性分布与正常人不一致（χ２＝３．１９，Ｐ＜０．０５）；红细胞免疫功能及ＳＯＤ酶活性较正常人明显降低（Ｐ＜０．０１）；β－内啡肽较正常人明显升高（Ｐ＜０．０１）。同时还发现肺癌患者的红细胞粘附肿瘤细胞功能与ＳＯＤ酶活性呈正相关（ｒ＝０．３９．Ｐ＜０．０５）。结论肺癌患者红细胞免疫功能低下；ＳＯＤ酶活性降低；β－内啡肽含量升高有部分与红细胞ＣＲ１基因密度型改变有关     

白细胞共同抗原(CD45)在可逆性大脑中动脉阻塞时大鼠脑组织的表达

阻塞大脑中动脉２ ｈ，再灌流０．５～４８ ｈ 制成脑缺血模型，用免疫组织化学技术观察了脑缺血后白细胞共同抗原在脑组织的表达。结果表明：白细胞共同抗原阳性的小胶质细胞或巨噬细胞呈圆形，未见分支型小胶质细胞，阳性的小胶质细胞于再灌流３ ｈ 开始出现，再灌流１２ ｈ 数量显著增多，并且胞质、胞核均为强阳性；阳性的小胶质细胞分布于纹状体、下丘脑、杏仁核处及皮质与外囊相连处，完全坏死区无阳性小胶质细胞；此外，同侧微血管强表达白细胞共同抗原；同侧大脑皮质Ⅳ、Ⅴ、Ⅵ层锥体细胞、丘脑、海马形态正常的神经元亦强表达白细胞共同抗原，但核固缩的神经元白细胞共同抗原则呈阴性。本实验推测白细胞共同抗原可能有保护神经元的作用，并可能是神经元与小胶质细胞之间的信息传递分子。     

A neuronal population in hypothalamus that dramatically resists acute ischemic injury compared to neocortex

Pyramidal neurons (PyNs) of the cortex are highly susceptible to acute stroke damage, yet "lower" brain regions like hypothalamus and brain stem better survive global ischemia. Here we show for the first time that a "lower" neuron population intrinsically resists acute strokelike injury. In rat brain slices deprived of oxygen and glucose (OGD), we imaged anoxic depolarization (AD) as it propagated through neocortex or hypothalamus. AD, the initial electrophysiological event of stroke, is a front of depolarization that drains residual energy in compromised gray matter. The extent of AD reliably determines ensuing cortical damage, but do all CNS neurons generate a robust AD? During 10 min of OGD, PyNs depolarize without functional recovery. In contrast, magnocellular neuroendocrine cells (MNCs) in hypothalamus under identical stress generate a weak and delayed AD, resist complete depolarization, and rapidly repolarize when oxygen and glucose are restored. They recover their membrane potential, input resistance, and spike amplitude and can survive multiple OGD exposures. Two-photon microscopy in slices derived from a fluorescent mouse line confirms this protection, revealing PyN swelling and dendritic beading after OGD, whereas MNCs are not injured. Exposure to the Na(+)-K(+)-ATPase inhibitor ouabain (100 μM) induces AD similar to OGD in both cell types. Moreover, elevated extracellular K(+) concentration ([K(+)](o)) evokes spreading depression (SD), a milder version of AD, in PyNs but not MNCs. Therefore overriding the pump by OGD, ouabain, or elevated [K(+)](o) evokes a propagating depolarization in higher gray matter but not in MNCs. We suggest that variation in Na(+)-K(+)-ATPase pump efficiency during ischemia injury determines whether a neuronal type succumbs to or resists stroke.     

急性应激大鼠脑边缘系统生化病理变化

目的 :探讨急性应激时NO等自由基对脑损害作用及超微结构的影响。方法 :建立急性应激大鼠模型 ,分别取边缘系统额叶、海马、下丘脑组织 ,电镜观察神经细胞超微结构变化、测定组织匀浆NO含量和SOD活力。结果 :急性应激组大鼠额叶、海马及下丘脑SOD活力均高于对照组 (P <0 0 5 ) ,NO含量在海马、下丘脑升高明显 (P <0 0 5 ) ,光镜和电镜下的海马、下丘脑神经细元减少 ,核仁碎裂、胞质内细胞器减少。结论 :急性应激脑组织NO含量和SOD活力增高 ,可对边缘系统下丘脑、海马造成损害。这可能是应激反应过度的病理生理学基础     

Effect of tibolone administration on central and peripheral levels of allopregnanolone and beta-endorphin in female rats

OBJECTIVE: We evaluated the effects of tibolone oral administration on neuroendocrine function by investigating the modulation exerted by tibolone administration on allopregnanolone and central and peripheral beta-endorphin (beta-EP) levels in ovariectomized rats. DESIGN: Female Wistar rats (N = 64) were included: 48 rats were ovariectomized, 8 cycling rats were included as controls, and 8 cycling rats were treated with placebo. The ovariectomized animals were divided into six groups: untreated rats and those that received 14-day oral treatment with either placebo, estradiol valerate (E2V) 0.05 mg/kg/d, or tibolone (0.1, 0.5, or 2 mg/kg/d. beta-EP levels were assessed in the frontal lobe, parietal lobe, hippocampus, hypothalamus, anterior pituitary, neurointermediate pituitary, and plasma, whereas allopregnanolone levels were measured in the frontal lobe, parietal lobe, hippocampus, hypothalamus, anterior pituitary, adrenal glands, and serum. RESULTS: The administration of tibolone (0.5 and 2 mg/kg/d) in ovariectomized rats induces a significant increase of allopregnanolone in the frontal lobe, parietal lobe, hippocampus, hypothalamus, whereas in serum a significant increase of allopregnanolone occurs only with the dose of 2 mg/kg/d, a significant decrease in allopregnanolone levels occurs in the adrenal glands. No changes occurred in the anterior pituitary. Tibolone doses of 0.5 and 2 mg/kg/d induced a significant increase in beta-EP content in the frontal lobe, hypothalamus, and neurointermediate lobe; and, at doses of 2 mg/kg/d, in the parietal lobe, anterior pituitary, and plasma, without changes in the hippocampus. Compared with E2V, 0.5 mg/kg/d tibolone showed a similar effect on allopregnanolone and beta-EP in most brain regions. CONCLUSIONS: Tibolone administration affects beta-EP and allopregnanolone levels, playing a role as a neuroendocrine modulator.     

c-fos和神经营养因子在大鼠脑缺血再灌流时的神经元表达特点

为了观察脑缺血再灌流时 c-fos和神经营养因子在神经元表达的时空特点 ,探讨其在缺血性神经元损伤中的作用 ,本研究用阻塞 SD大鼠大脑中动脉 2 h、再灌流 0 .5～ 48h制成局灶性脑缺血模型 ,用免疫组化方法观察了 c-fos和神经营养因子转化生长因子、神经生长因子和胶质源性神经营养因子在神经元的表达特点。结果表明 ,c-fos和转化生长因子分布相似 ,正常组无 c-fos和转化生长因子阳性神经元 ;缺血再灌流 0 .5～ 48h阳性的神经元主要位于非大脑中动脉供血区 ,缺血区皮质、纹状体和视前区神经元为阴性。而实验各组对照侧皮质神经元中等阳性。神经生长因子、胶质源性神经营养因子在缺血脑组织的分布相似。正常组、假性手术组 ,皮质、嗅结节、丘脑和下丘脑等区的神经元神经生长因子、胶质源性神经营养因子免疫反应为弱阳性乃至强阳性 ;再灌流 0 .5 h,缺血区皮质弱阳性 ,缺血周边区中等阳性 ;再灌流 3～ 48h,神经生长因子、胶质源性神经营养因子强阳性的神经元主要位于非大脑中动脉供血区和缺血周边区。此外 ,对照侧皮质大量的神经元呈强阳性。结论 ,上述资料提示即早基因 c-fos和神经营养因子具有促进神经元存活的作用     

Conjugated equine estrogens,estrone sulphate and estradiol valerate oral administration in ovariectomized rats: effects on central and peripheral allopregnanolone and beta-endorphin

OBJECTIVES: Several natural or synthetic estrogenic molecules are commonly used in oral hormone replacement therapy for the relief of menopausal complaints and for the primary prevention of cardiovascular disease and osteoporosis. Little information is available concerning the comparative efficacy of different compounds on neuroendocrine function. The opioid peptide beta-endorphin (beta-EP), and the neurosteroid allopregnanolone are considered markers of neuroendocrine function and their synthesis and action is regulated by gonadal steroids. The present study aimed to investigate the effects of a 2-week oral treatment with estradiol valerate (EV), estrone sulphate (ES), or conjugated equine estrogen (CEE) on central and peripheral beta-EP and allopregnanolone levels in ovariectomized (OVX) female rats. METHODS: Twelve groups of Wistar OVX rats received oral EV (0.05, 0.1, 0.5 and 1 mg/Kg/day) or ES (0.1, 0.5, 1 and 2 mg/Kg/day), or CEE (0.1, 0.5, 1 and 2 mg/Kg/day) for 14 days. One group of fertile and one group of OVX rats were used as controls. beta-EP content was assessed in hypothalamus, hippocampus, anterior and neurointermediate pituitary, and plasma, while allopregnanolone content was assessed in hypothalamus, hippocampus, anterior pituitary, adrenals and serum. RESULTS: Ovariectomy induced a significant decrease in beta-EP and allopregnanolone content in hypothalamus, hippocampus, pituitary, and serum, while it increased allopregnanolone content in the adrenals. In OVX rats, the administration of each molecule reversed the ovariectomy-induced beta-EP and allopregnanolone changes in a dose-dependent fashion, therefore completely restoring their concentration. At higher doses, the estrogenic compounds induced significantly higher levels of allopregnanolone and beta-EP than in fertile rats. CEE induced higher allopregnanolone levels in hypothalamus, anterior pituitary and serum than the other estrogenic molecules, and in the hippocampus with respect to EV alone. CEE produced higher beta-EP levels in the hippocampus and hypothalamus with respect to EV and ES. CONCLUSION: In the examined tissue and serum estrogens restore the ovariectomy induced changes in allopregnanolone and beta-EP content in a dose-dependent manner; the magnitude of these effects is not uniform and it is related to the different tissues and the employed compounds.     

Functional response of hippocampal CA1 pyramidal cells to neonatal hypoxic-ischemic brain damage

Perinatal hypoxic-ischemic (H-I) is a major cause of brain injury in the newborn. The hippocampus is more sensitive to H-I injury than the other brain regions. It is believed that H-I brain damage causes a loss of neurons in the central nervous system. The patterns of neuronal death include apoptosis and necrosis. With regard to the responses of neurons, the neural functional changes should be earlier than the morphologic changes. The aim of the present study is to evaluate the electrophysiological characteristics and the synaptic transmission functions. Seven-day-old Sprague-Dawley rat pups were randomly divided into sham operation and H-I groups. The patch clamp, immunohistochemistry and Western blotting techniques were used to achieve this objective. The results of the study showed a decrease in neuronal excitability and a significant increase in the frequency of spontaneous excitatory postsynaptic currents and the duration of EPSCs in the CA1 pyramidal cells of H-I brain damage rats. The glutamate transporter subtype 1 (GLT-1) expression level of the hippocampal CA1 area in the H-I group was decreased compared with the control. There was no difference in the amplitude of excitatory postsynaptic currents and should be no difference in the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR), N-methyl-d-aspartate receptor (NMDAR) and synaptophysin between the control and H-I brain injury group. These results revealed that changes of electrophysiological characteristics and synaptic functions occur instantly after H-I brain damage in the hippocampal pyramidal cells of neonatal rats. The failure to eliminate glutamate should be one of the important factors of excitotoxicity injury on hippocampal CA1 pyramidal cells, while neuronal excitation was not increased in the H-I brain injury model.     

毒蕈碱M2受体在脑震荡大鼠脑内的表达变化

为了探讨脑震荡(brain concussion,BC)后认知功能障碍的大鼠中枢毒蕈碱M2受体的表达变化,本实验应用金属单摆式机械打击装置复制单纯性脑震荡大鼠模型,采用免疫组织化学结合图像分析的方法,观察BC后大脑前额叶皮质(PFC)、海马CA1-CA4区、丘脑、尾壳核(CPU)、Broca斜角带垂直支(VDB)和内侧隔核(MSN)区M2受体蛋白的表达情况。结果显示:在损伤后M2受体蛋白的表达在海马CA1-CA4区出现轻微下降(P>0.05),在PFC、VDB、CPU和MSN区即刻呈轻度上升,随后又下降,但与正常组相比无显著性差异(P>0.05);在伤后1、8、24d组大鼠丘脑M2受体的表达呈明显下降,与正常对照组比较有显著性差异(P<0.05)。以上结果提示M2受体的表达在丘脑出现明显下调的改变可能与BC认知功能的改变有关。     

复方丹参对大鼠脑缺血再灌注后大脑皮层神经细胞凋亡和Bcl-2 mRNA表达的影响

为了探讨中药复方丹参对大鼠局灶性脑缺血再灌注后大脑皮层神经细胞凋亡及Bcl-2mRNA表达的影响和保护作用,本研究采用大脑中动脉内栓线阻断法(MCAO)造成局灶性脑缺血再灌注模型,应用原位末端标记(TUNEL)和原位杂交技术检测大鼠大脑皮层神经细胞凋亡和神经细胞Bcl-2mRNA的表达,并进行图像分析。结果显示:缺血再灌注组凋亡神经细胞主要位于缺血侧大脑皮层缺血边缘区(半暗区);缺血侧大脑皮层缺血边缘区神经细胞Bcl-2mRNA的表达在缺血再灌注2h后升高,随着缺血再灌注时间的延长逐渐增强;复方丹参保护组神经细胞Bcl-2mRNA的表达明显强于缺血再灌组(P<0.01),凋亡神经细胞数明显低于缺血再灌组(P<0.01)。上述结果说明复方丹参可通过上调神经细胞Bcl-2mRNA的表达,抑制神经细胞凋亡,减轻缺血再灌注对大鼠大脑皮层神经细胞的损伤。     

Neuronal injury after photoactivation of photofrin II.

Photodynamic therapy has been used in the management of patients with malignant brain tumors even though the effects of this form of treatment on the adjacent normal brain are incompletely characterized. The authors examined, in sequential experiments, morphologic alterations affecting the cerebral cortex in rats injected with Photophrin II and exposed to light. Initially, minimal cell alterations, including cisternal swelling of both endoplasmic reticulum and Golgi apparatus, involved only neurons located in the superficial layers of the cerebral cortex exposed to light. These changes spread, over a period of several hours, from the surface to the bottom of the cortex and eventually involved the entire cortical segment exposed to light. The earliest structural signs of lethal injury to neurons developed over a period of 18 hours after porphyrins had been photoactivated and astrocytes had been severely damaged. Signs of lethal injury to neurons included an increase in the number of mitochondrial cristae and appearance of amorphous electron-dense deposits within swollen mitochondria. The appearance of these alterations was followed by segregation of intracytoplasmic organelles and fragmentation of nuclear and cytoplasmic membranes. The tissue changes, including those involving neurons, eventually progressed to coagulation necrosis at 48 hours. These observations suggest that prophyrins injected to rats (48 hours before photoactivation) cause swelling and necrosis of astrocytes. This is followed by neuronal necrosis, which appears at two time intervals; the initial neuronal necrosis occurs after the astrocytic disintegration. A second type of neuronal alteration appears after microvessels become thrombosed and ischemia is likely to develop.