藏药旺拉提取物对东莨菪碱致动物学习记忆障碍的改善作用及机制研究

观察藏药旺拉提取物（CE）对东莨菪碱致动物学习记忆障碍的改善作用并研究其作用机制。采用腹腔注射东莨菪碱造模,以跳台法测定小鼠的学习记忆能力,以电生理方法测定大鼠海马长时程增强（LTP）的诱导, 分别以生化及放射性同位素分析法测定脑匀浆中乙酰胆碱酯酶（AChE）及胆碱乙酰转移酶（ChAT）的活性。结果表明,模型动物跳下平台的潜伏期明显缩短,LTP诱导受抑制。灌胃给予CE（5、10及20 mg·kg^-1）可改善模型小鼠在跳台中的表现,腹腔注射CE（5 mg·kg^-1）可逆转东莨菪碱对大鼠LTP诱导的抑制。此外,CE可显著增强ChAT活性,而对AChE活性无显著影响。CE可改善东莨菪碱致小鼠学习记忆障碍,其作用可能与改善海马LTP诱导及增强ChAT活性有关。
      

Enhancement of the nonamyloidogenic pathway by exogenous NGF in an Alzheimer transgenic mouse model

Nerve growth factor (NGF) is an important nerve cell growth regulatory factor and has an indispensable role in the development, survival and regeneration of the cholinergic basal forebrain (CBF) neurons, and it has multiple targets when used for Alzheimer’s Disease (AD) therapy. In this study, we observed whether NGF can affect cholinergic neurons to change amyloid-β precursor protein (APP) metabolism process and reduce amyloidosis in AD brains. NGF was administered intranasally to APP/PS1 double-transgenic mice for 14 weeks. We observed an increase in APP695 and ADAM10 and a decrease in BACE1 and PS1 protein levels and, subsequently, a reduction in Aβ1–40 and Aβ1–42 levels and Aβ burden were present in NGF-treated mice brains, suggesting that NGF enhanced the APP nonamyloidogenic cleavage pathway and reduced the Aβ generation in the APP/PS1 transgenic mice brains.     

（N-[18F]氟甲基）胆碱的合成与质量控制

目的：研究（N-[18F]氟甲基）胆碱（18F-FCH）在日本住友氟碳氮三合一合成装置上的全自动化合成与质量控制。方法由日本住友回旋加速器生产出来的18F-与CH2Br2反应生成中间产物18FCH2Br，在高温下通过Ag-Triflate/C柱对其活性进行改造，生成活性更强的18FC2H4SO3CF3，再与N, N-二甲基乙醇胺在Sep-Pak C-18柱上常温进行反应，分别用酒精、注射用水、生理盐水淋洗串联在一起的Sep-Pak C-18柱和Sep-Pak CM柱后纯化得到成品。通过高效液相色谱法对合成产品的放化纯度进行检测。结果合成产品的放化纯度＞97%，未校正放化收率为27%，合成耗时38 min。结论此种合成方法过程简单、操作容易、产品质量稳定，并且合成效率及放化纯度均有所提高。     

参乌胶囊对东莨菪碱模型大鼠学习记忆能力和脑内胆碱能系统的影响

目的观察中药新复方参乌胶囊对东莨菪碱致记忆障碍模型大鼠学习记忆及脑内胆碱能系统的影响。方法将Wistar大鼠随机分为对照组、东莨菪碱模型组、多奈哌齐组(阳性对照药)、参乌胶囊小剂量(0.2g.kg-1)、中剂量组(0.6g.kg-1)、大剂量(1.8g.kg-1)6组,灌胃给药2周后,除正常对照组腹腔注射生理盐水外,其他各组注射东莨菪碱2mg.kg-1,20min后进行Morris水迷宫和跳台测试,测试结束后处死,取其脑皮层、海马,应用生化方法测定乙酰胆碱酯酶(AChE)活性,放射免疫法测定胆碱乙酰基转移酶(ChAT)活性,放射配基法测定M受体结合力。结果参乌胶囊灌胃给药能够提高东莨菪碱模型大鼠学习记忆能力,缩短Morris水迷宫游泳时间及距离,延长跳台实验的潜伏期,减少错误次数(P<0.05);并能降低模型大鼠脑皮层AChE活性,提高海马ChAT活性,增强皮层和海马M受体结合力(P<0.05,P<0.01)。结论参乌胶囊可以改善东莨菪碱模型大鼠的记忆障碍,其机制可能与提高M受体结合力、增强ChAT活性、抑制AChE活性有关。     

针炙治疗胆碱能性荨麻疹（遇热型）一例

胆碱能性荨麻疹，是当运动、受热、精神紧张后，胆碱能性神经未梢兴奋并释放乙酰胆碱，引发机体过敏。西医对此尚无特效疗法，多采用内服抗组胺药物、皮质激素类药物临时抑制为主，长时间应用在停药后易引起药物反弹。中医通运对经络和穴位的研究，运用针刺的的方法能使丘脑产生和分泌有效阻断热敏神经元效果的多肽、继而达到降低胆碱能性神经未梢兴奋阀值和减轻机体对过敏原的应激反应。     

Effect of repeatedly given CDP‐choline on cardiovascular and tissue injury in spinal shock conditions: investigation of the acute phase

Objectives The protective effect of CDP‐choline in spinal cord transection and the mediation of its cardiovascular effects were investigated. Methods Spinal cords of rats were transected at the T1–T2 levels. CDP‐choline (250 mg/kg; intravenous) was administered 2 h and/or 24 h after the injury. Key findings Spinal cord transection caused severe tissue damage, decreased mean arterial pressure, heart rate, plasma adrenaline, and noradrenaline but increased plasma vasopressin levels. Repeated CDP‐choline treatment attenuated the degree of tissue injury. Administration of CDP‐choline at 2 h after transection transiently increased blood pressure and decreased heart rate, while it produced a small decrease in blood pressure and heart rate when it was given at 24 h. Plasma adrenaline levels were higher in the group where CDP‐choline was given repeatedly. Plasma noradrenaline and vasopressin levels did not change additionally after CDP‐choline injections in all groups. In order to determine if CDP‐choline attenuates the oxidative injury induced by transection, we measured blood superoxide dismutase, glutathione peroxidase activity and malondialdehyde levels. Repeated CDP‐choline administration decreased blood superoxide dismutase and glutathione peroxidase activity without any effect on malondialdehyde levels. Conclusions Data indicate that repeated intravenous CDP‐choline treatment prevents tissue damage in spinal shock conditions in the acute phase. The cardiovascular effects of the drug do not seem to be responsible for this protection but the drug‐induced attenuation of the oxidative stress may play a role.     

Additive and synergistic effects of fetal nicotine and dexamethasone exposure on cholinergic synaptic function in adolescence and adulthood: Implications for the adverse consequences of maternal smoking and pharmacotherapy of preterm delivery

Maternal smoking contributes to preterm delivery; glucocorticoids are the consensus treatment for prematurity, thus producing fetal coexposure to nicotine and dexamethasone. We administered nicotine to pregnant rats throughout gestation at a dose (3 mg/kg/day) producing plasma levels typical of smokers. Later in gestation, animals received dexamethasone (0.2 mg/kg). We assessed developmental indices for acetylcholine (ACh) synaptic function throughout adolescence, young adulthood and later adulthood, evaluating brain regions possessing major ACh projections and cell bodies; we measured choline acetyltransferase activity, hemicholinium-3 binding to the presynaptic choline transporter and nicotinic ACh receptor binding. In general, nicotine and dexamethasone, alone or in combination, produced regionally-selective increases or decreases in choline acetyltransferase activity but larger, consistent elevations in hemicholinium-3 and nicotinic ACh receptor binding; the patterns were indicative of ACh synaptic hyperactivity. Superimposed on these overall effects, there were significant disparities in temporal and regional relationships among the different treatments, notably involving effects that emerged later in life, after a period of apparent normality. This indicates that nicotine and dexamethasone do not simply produce an initial ACh neuronal injury that then persists throughout the lifespan but rather, they alter the developmental trajectory of ACh function. Most importantly, the combined exposure to nicotine + dexamethasone elicited greater changes than either of the individual exposures, involving both additive and synergistic effects. Our results thus point to potentially worse neurobehavioral outcomes of the pharmacotherapy of preterm labor in the offspring of smokers.