β—内啡肽增强谷氨酸神经毒性

探讨β－内啡肽对谷氨酸单钠诱导的神经毒性的影响。方法：形态学观察、神经元面积图象分析、线粒体膜蛋白结合钙和单细胞内游离钙浓度测定。结果：β－内啡肽在０．５－５．０ｍｇ·ｋｇ＾－１范围内以剂量依赖方式加剧谷氨酸单钠诱导的下丘脑弓状核神经元损伤，谷氨酸单钠诱导的线粒体膜蛋白结合钙增多可以被β－内啡肽２ｇ·Ｌ＾－１加强，谷氨到单钠诱导的单细胞内钙浓度升高也被β－内啡肽２ｇ·Ｌ＾－１从３２０±８４提高至５     

吗啡增强谷氨酸单钠神经毒性及其作用机制

用皮层神经细胞体外培养、形态学观察、单个神经细胞内游离钙检测及乳酸脱氢酶(LDH)测定等方法,观察了吗啡对谷氨酸单钠(MSG)神经毒性增强作用以及纳洛酮对吗啡作用的逆转,分析了其可能的作用机制。结果表明:吗啡能显著增强的MSG的细胞毒作用.纳络酮可逆转这种增强作用,细胞内Ca²⁺超载可能是兴奋性神经毒素引起神经元死亡的共同病理学机制。     

大鼠侧脑室注射Ad-NEP对大鼠脑脊液β-内啡肽的影响

目的 探讨大鼠侧脑室注射不同滴度表达β-内啡肽的重组腺病毒(Ad-NEP)对脑脊液β-内啡肽的影响.方法 选择雄性SD大鼠36只随机均分为6组:A、B、C、D和E组,分别于侧脑室注射滴度为5×107、5×108、5×109、5×1010和5×1011噬菌斑形成单位(PFU)的Ad-NEP;F组作为空白对照.4d后测定脑脊液中β-内啡肽的浓度.结果 C组和D组脑脊液中β-内啡肽的浓度明显高于F组[(667.80±121.50) pg/ml和(974.65±174.97) pg/ml vs.(76.20±7.13) pg/ml](P＜0.01).结论 使用5×109和5×1010PFU两种滴度的Ad-NEP侧脑室注射是提高实验大鼠脑脊液β-内啡肽浓度的较好选择.     

β-内啡肽对更年期妇女血管功能的影响

目的 探讨更年期妇女外周血浆β-内啡肽水平的变化对其血管功能的影响.方法 将101例更年期妇女(45岁～60岁),根据症状、血压、绝经情况进行分组,各组妇女均进行外周血浆β-EP和一些相关指标测定[血栓素A2(TXA2)和前列环素(PGI2)].结果 ①有血管舒缩紊乱症状(如潮热、头晕)的妇女组β-EP水平低于无症状妇女组,与对照组比较有显著差异(P＜0.002,P＜0.05).②围绝经期妇女β-EP水平的变化对血压无显著影响(P＞0.05).③围绝经期妇女血浆β-EP水平的变化对TXA2和PGI2的水平及比值均无明显影响.结论 围绝经期妇女β-EP水平变化可能会引起神经内分泌功能的紊乱,暂时性地影响更年期妇女的血管舒缩功能,但对血压及血管因子无明显影响.     

大鼠脑出血周边组织谷氨酸、β-内啡肽(β-EP)含量及细胞凋亡的变化与纳络酮关系的影响

目的:研究纳络酮对大鼠脑出血周边组织谷氨酸(Glu)、β-内啡肽(β-EP)含量及细胞凋亡的影响.方法:Wistar大鼠112只,随机分为脑出血组,脑出血+纳络酮(FDPM)组,两组各分为(出血前,出血后4h、6h、12h、24h、72h、7d)7个时间点.利用化学方法测定大鼠脑出血周边组织Glu含量,采用放免技术检测脑出血周边组织β-EP含量;利用原位末端标记法测定出血周边组织中神经细胞的凋亡情况.结果:大鼠脑出血后4h血肿周边脑区Glu含量开始升高(P<0.01),在血肿形成的高峰期12h达峰值;大鼠脑出血后4h血肿周边脑区β-EP含量开始升高(P<0.05)在血肿形成的高峰期72h达峰值.大鼠脑出血周边组织6h出现凋亡细胞,12h上升显著(P<0.01),3d凋亡细胞达峰值,7d时仍存在较多凋亡细胞.纳络酮干预后Glu、β-EP含量,凋亡细胞数量与脑出血组对应时间点比较显著下降(P<0.01).结论:大鼠脑出血周边组织Glu、β-EP含量增高,脑出血周边组织神经细胞存在长时间凋亡,Glu、β-EP可以促进其凋亡;纳络酮干预后Glu、β-EP含量降低,纳络酮减少大鼠脑出血周边组织神经细胞凋亡.     

β-内啡肽在中枢吗啡预处理减轻大鼠心肌缺血后损伤中的作用

目的观察中枢与外周β-内啡肽对缺血后心肌的影响及其在侧脑室吗啡预处理减轻大鼠心肌缺血/再灌注损伤中的含量变化,探讨β-内啡肽在中枢吗啡预处理在体大鼠缺血后心肌保护作用中的角色。方法66只♂SD大鼠,分别建立侧脑室微量注射和心肌缺血/再灌注损伤动物模型。随机分为假手术(Sham)组、缺血对照(CON)组、缺血预处理(IPC)组、中枢和外周β-内啡肽激动剂(Icv/Iv-EP)组、中枢吗啡预处理(MPC组)、中枢β-内啡肽阻断剂(Icv-MPC-Anti-EP/Icv-Anti-EP-MPC)组、外周β-内啡肽阻断剂(Icv-MPC+Iv-Anti-EP)组、中枢和外周β-内啡肽阻断剂自身对照(Icv/Iv-Anti-EP)组。观察平均动脉压(MAP)、心率(HR)、压力心率乘积(RPP)、缺血危险区(AAR)、梗死区(IS)体积、IS/AAR等的变化;同时以免疫组化观察下丘脑弓状核(arcuate nucleus,ARC),中脑导水管周围灰质(periaque-ductalgray,PAG)及左室心肌(myocardium of left ventricle,MC)β-内啡肽的阳性表达。结果与CON组相比,IPC、MPC、Icv-EP、Iv-EP、Icv-Anti-EP-MPC、Icv-MPC+Iv-Anti-EP组均明显降低IS/AAR(P<0.01);Icv-MPC-Anti-EP组虽然取消MPC的保护效应(P<0.01),但较CON组差异仍有统计学意义(P<0.05);与CON组相比,MPC组减弱了ARC中β-内啡肽的阳性表达(P<0.05),同时明显增强PAG和左室心肌的免疫反应强度(P<0.05;P<0.01)。结论中枢与外周β-内啡肽对缺血后心肌损伤有保护作用;侧脑室吗啡预处理后可能促进下丘脑弓状核释放β-内啡肽,后者作为神经递质部分参与了中枢吗啡预处理介导的心肌保护效应。     

纳洛酮对敌敌畏中毒家兔血浆β-内啡肽含量的影响

目的 研究纳洛酮对敌敌畏中毒家兔血浆β-内啡肽含量的影响.方法 将家免分为两组,均采用敌敌畏灌胃法使其中毒,常规治疗组予硫酸阿托品和碘解磷定治疗,纳洛酮预防组在中毒前予纳洛酮,中毒后予硫酸阿托品和碘解磷定治疗,分别测定两组动物敌敌畏中毒前和中毒治疗后不同时间血浆β-内啡肽含量.结果 与正常动物相比,常规治疗组血浆β-内啡肽水平在中毒治疗后1～20 h均显著升高(P<0.001);与常规治疗组相比,纳洛酮预防组血浆β-内啡肽水平在中毒治疗后1～20 h均显著降低(P<0.01).结论 家兔急性敌敌畏中毒可引起血浆β-内啡肤水平急剧升高,纳洛酮预防性应用则可明显降低中毒家兔血浆β-内啡肽水平.     

纳洛酮对急性酒精中毒患者血浆β-内啡肽水平的影响

目的观察纳洛酮对急性酒精中毒患者血浆β-内啡肽水平的影响。方法将85例急性酒精中毒患者随机分为2组,对照组42例,采用补液利尿常规治疗;实验组43例,在常规治疗的基础上,采用纳洛酮治疗,比较两组疗效和治疗前后1h、2h血浆β-内啡肽水平。结果实验组的治疗持续时间明显短于对照组(P<0.01),治疗后血浆β-内啡肽水平明显低于对照组(P<0.01)。结论纳洛酮能够降低血浆β-内啡肽的水平,用于治疗急性酒精中毒安全有效。     

Enhancing effects of β-endorphin on glutamate neurotoxicity

目的：探讨β内啡肽对谷氨酸单钠诱导的神经毒性的影响．方法：形态学观察、神经元面积图象分析、线粒体膜蛋白结合钙和单细胞内游离钙浓度测定．结果：β内啡肽在０５－５０ｍｇ·ｋｇ－１范围内以剂量依赖方式加剧谷氨酸单钠诱导的下丘脑弓状核神经元损伤，谷氨酸单钠诱导的线粒体膜蛋白结合钙增多可以被β内啡肽２ｇ·Ｌ－１加强，谷氨酸单钠诱导的单细胞内钙浓度升高也被β内啡肽２ｇ·Ｌ－１从３２０±８４提高至５８９±７８ｎｍｏｌ·Ｌ－１．结论：β内啡肽以剂量依赖方式通过加剧胞内钙自稳态失衡来增强谷氨酸单钠诱导的神经毒性．     

谷氨酸单钠损毁弓状核对雌性大鼠骨组织形态计量学的实验研究

目的 观测EPO治疗大鼠面神经损伤后对面神经核神经元凋亡的的影响,探讨EPO促进神经再生与修复的机理.方法 96只SD大鼠随机分成4组.利用神经卡压法损伤面神经,每组在术后第7d,14d,21d和28d四个时间点取材,尼氏染色和免疫组织化学方法对面神经核神经元进行染色并定量分析.结果 经EPO治疗后,大鼠面神经核内凋亡抑制基因Bcl-2明显增多,细胞凋亡明显减少,EPO组明显优于对照组(P<0.01).结论 EPO有效提高周围神经损伤后的神经核内凋亡抑制基因的含量的表达,减少神经元凋亡,促进神经的再生与神经功能的恢复.     

谷氨酸神经细胞毒作用的新途径——谷氨酸/胱氨酸转运体介导机制

谷氨酸是中枢神经系统主要的兴奋性神经递质 ,与许多神经系统疾病有密切关系。谷氨酸除通过激活谷氨酸受体产生兴奋性神经毒性外 ,还可通过抑制细胞膜上谷氨酸 /胱氨酸转运体的功能产生细胞毒性作用 ,该作用以细胞内谷胱甘肽耗竭和活性氧成分升高为主要特征 ,被称为谷氨酸的氧化毒性 ,对许多神经系统疾病的治疗具有重要意义。     

Effects of morphine, beta-endorphin and naloxone on catecholamine levels and sexual behavior in the male rat

Intraperitoneal administration of the opiate antagonist naloxone hydrochloride (30 mg/kg) to sexually experienced male rats caused a significant reduction in mount and intromission latencies, number of mounts preceding ejaculation and ejaculation latencies. Intraperitoneal adminstration of naloxone (30 mg/kg) also stimulated persistant non-copulators to begin mating and to ejaculate within a twenty minute test period. Conversely, intraperitoneal administration of morphine sulphate (6 mg/kg) as well as intraventricular injection of the endogenous opiate beta-endorphin (6 micrograms) produced a complete loss of copulatory behavior in male rats. The deficit in sexual behavior induced by beta-endorphin was correlated with a significant increase in hypothalamic norepinephrine levels. It is suggested that the endogenous opiates may be involved in the mediation of sexual behavior via an interaction with central catecholaminergic systems.     

Dynorphin: a possible modulatory peptide on morphine or beta-endorphin analgesia in mouse

Dynorphin-(1-13), but not dynorphin-(1-9) has been shown to have significant effects on opiate and beta-endorphin-induced analgesia despite not having any appreciable analgesic activity itself. Dynorphin had no effect on Sandoz FK33824 compound-induced analgesia.     

Biphasic effects of chronic nicotine treatment on hypothalamic immunoreactive beta-endorphin in the mouse

Hypothalamic but not pituitary immunoreactive beta-endorphin (beta-E) was significantly reduced (37%) in mice 24 hr following 30 daily doses of nicotine (1200 micrograms/kg, SC). Hypothalamic beta-E returned towards normal levels within 7 days and was observed to rise 50% above normal 14 days after the cessation of nicotine treatment. None of the other neuropeptides measure, substance P, neurotensin, or [met5]-enkephalin was altered by nicotine treatment. The data suggest that the hypothalamic beta-E containing neurons were unable to adapt to nicotine's repeated effects on this system.     

谷氨酸转运体、谷氨酸/胱氨酸转运体与谷氨酸神经细胞毒作用

谷氨酸转运体与谷氨酸／胱氨酸转运体在脑缺血疾病中起重要作用，谷氨酸转运体的结构或功能改变可使细胞间隙的谷氨酸浓度急剧升高，激活NMDA受体产生一系列的表现，同时抑制谷氨酸／胱氨酸转运体对胱氨酸的摄取，介导谷胱苷肽耗竭、氧自由基升高、胞内钙升高、线粒体损伤、细胞色素c释放等神经细胞毒环节，激活半胱天冬酶诱导凋亡。可进一步加重谷氨酸的神经细胞毒作用。     

Release of beta-endorphin from rat hypothalamus in vitro.

The rate of release of beta-endorphin-like immunoreactivity (beta-EI) from rat hypothalamic slices was increased 3- to 4-fold over the spontaneous release during exposure to a depolarizing concentration of potassium ions. This augmented outflow was abolished in the absence of calcium. The amount of beta-EI released from slices exposed to a second pulse of potassium was reduced by approximately 50% compared to that in the first. 70% of the potassium-induced released immunoreactive material migrated on a calibrated Sephadex G-50 column like synthetic human beta-endorphin. These findings are discussed in terms of a neuronal release of beta-endorphin and may be taken as supportive evidence for a neurotransmitter and/or neurohormonal role of beta-endorphin in the hypothalamus.     

6-羟基多巴的细胞毒作用与谷氨酸转运的关系

目的探讨6-羟基多巴(6-OHDA)导致细胞毒性与谷氨酸(glutamate,Glu)递质水平和谷氨酸转运体的相关性。方法大鼠脑黑质内定位注射6-OHDA,制备帕金森病(Parkinson's disease,PD)动物模型;用在体微透析技术收集大鼠纹状体细胞外液;用高效液相色谱法测定PD大鼠纹状体和PC12细胞的细胞外液中Glu的水平;用流式细胞仪和酶标仪检测细胞凋亡率和细胞活性;通过测定L-［³H］-Glu的摄取能力确定谷氨酸转运体的功能。结果6-OHDA诱导PC12细胞和大鼠损毁侧纹状体释放Glu增加,使PC12细胞凋亡和活性降低,而PC12细胞和突触体上的谷氨酸转运体功能显著下降。结论6-OHDA引起的神经毒性与其增加Glu释放和降低谷氨酸转运体功能有关。     

Effects of [Des-Tyr 1]-gamma-endorphin and alpha-endorphin on substantia nigra self-stimulation.

The β-lipotropin fragments, [des-Tyr¹]-γ-endorphin (DTγE, β-LPH_62–77) and α-endorphin (β-LPH_61–76) affect self-stimulating behavior associated with electrical stimulation of neurons of the ventral tegmentum area of rats in an opposite way. Subcutaneous administration of DTγE (5 and 25 μg) attenuated and that of α-endorphin (5 and 25 μg) facilitated this behavior. Similar opposite effects were observed after subcutaneous treatment with respectively the neuroleptic haloperidol (5 μg) and the psychostimulant amphetamine (100 μg). By using a biphasic testparadigm of decreasing and subsequent increasing the stimulating current intensity it was noted that the neuropeptides predominantly exerted their effect on responding at current intensities in the neighbourhood of the threshold for eliciting the behavior, whereas the neuroleptic and psychostimulant drug appeared to affect responding at currents associated with maximal performance as well. In contrast to haloperidol, the effectiveness of DTγE was of a long term nature, in that performance of the rat was still affected 24 hr after peptide treatment. The results support the hypothesis that DTγE in some aspects interacts with brain substrates in a way comparable to that of neuroleptics. The data further suggest that closely related fragments of β-lipotropin modulate on-going activity of in particular dopaminergic neuronal systems.     

APP17肽对谷氨酸引起神经毒作用的影响

目的　通过观察APP17肽和谷氨酸对人神经母细胞瘤株SY5Y生长及NT 3、NF表达的影响 ,初步证实APP17肽对谷氨酸引起的神经元毒性具有一定保护效应。方法　MTT代谢率、LDH漏出率测定、细胞计数 ,WesternBlot观察SY5YNT 3、NF表达。结果　谷氨酸可使MTT代谢率降低、细胞计数减少 ,LDH漏出率升高 ,NT 3、NF表达减少 ,加入APP17肽可使上述指标恢复或接近正常。结论　谷氨酸对神经元有毒性作用 ,而APP17肽可减轻这种损伤 ,对神经元产生保护作用。