鹿茸多肽对轻度认知功能障碍大鼠学习记忆能力的改善作用及其调节Keap1/Nrf2 /HO-1信号通路的机制

观察鹿茸多肽（VAP）对轻度认知功能障碍（MCI）模型大鼠学习和记忆能力及海马组织中KELCH状ECH相关蛋白1 （Keap1）/核因子E2相关因子2（Nrf2）/血红素氧合酶1（HO-1）信号通路相关蛋白表达的影响,并探讨其作用机制。     

Protective effect of ginsenoside Rh2 on scopolamine‐induced memory deficits through regulation of cholinergic transmission,oxidative stress and the ERK‐CREB‐BDNF signaling pathway

Rh2 is a rare ginsenoside and there are few reports of its effect on cognition compared with other similar molecules. This study aimed to establish the impact of Rh2 treatment on improving scopolamine (Scop)‐induced memory deficits in mice and illuminate the underlying mechanisms. First, memory‐related behavior was evaluated using two approaches: object location recognition (OLR), based on spontaneous activity, and a Morris water maze (MWM) task, based on an aversive stimulus. Our results suggested that Rh2 treatment effectively increased the discrimination index of the mice in the OLR test. In addition, Rh2 elevated the crossing numbers and decreased the escape latency during the MWM task. Moreover, Rh2 markedly upregulated the phosphorylation of the extracellular signal‐regulated kinase (ERK)‐cAMP response element binding (CREB)‐brain derived neurotrophic factor (BDNF) pathway in the hippocampus. Meanwhile, the administration of Rh2 significantly promoted the cholinergic system and dramatically suppressed oxidative stress in the hippocampus. Taken together, Rh2 exhibited neuroprotective effects against Scop‐induced memory dysfunction in mice. Rh2 activity might be ascribed to several underlying mechanisms, including its effects on modulating the cholinergic transmission, inhibiting oxidative stress and activating the ERK‐CREB‐BDNF signaling pathway. Consequently, the ginsenoside Rh2 might serve as a promising candidate compound for Alzheimer's disease.     

银杏叶提取物对东莨菪碱所致大鼠空间工作记忆障碍的影响

目的探讨银杏叶提取物对东莨菪碱所致大鼠空间工作记忆障碍的影响。方法将大鼠随机分成三组：正常组，东莨菪碱组和银杏叶治疗组，水迷宫试验，东莨菪碱组按0．4mg／kg腹腔注射，以后每天注射等体积生理盐水，连用1周。正常对照组每天注射与东莨菪碱等体积的生理盐水，连用1周。银杏叶治疗组按10mg／kg腹腔注射，每天1次，连用1周。1周后进行Morris水迷宫试验，观察3组大鼠平台逃避潜伏期，并与试验后第一天比较。结果两次逃避潜伏期在正常组差异有统计学意义（46．4±17．1，13．4±8．2，P〈0．001），东莨菪碱组无统计学意义（23．6±14．3，18．1±9．8，P〉0．05）。银杏叶组差异有统计学意义（27．9±14．3，9．0±3．8，P〈0．05）。结论M型胆碱能受体阻滞剂东莨菪碱能损害大鼠空间工作记忆，银杏叶提取物能改善这种损害，说明银杏叶提取物是通过影响胆碱能系统来发挥其促智作用的。     

改良桃胶的不同配伍对复杂成分均衡释放的影响

目的 阐明改良桃胶的不同配伍(用量、填充剂)对复杂成分均衡释放的影响.方法 以喘平方为模型药,改良桃胶为缓释辅料,采用体外释放度结合HPLC法,测定喘平缓释片的指标成分(麻黄碱、伪麻黄碱、东莨菪碱)释放度,计算累积释放曲线斜率(K)值,评价指标成分间是否均衡释放.结果 不同配伍考察中,当填充剂为淀粉、淀粉/糊精、淀粉/微晶纤维素(MCC)时,各指标成分K值接近,实现了均衡释放;而与糊精、MCC配伍时,K值差异较大,无法均衡释放.随着改良桃胶辅料用量的增加,释药时间延长,指标成分的K值基本一致,达到均衡释放.结论 不同填充剂与改良桃胶配伍,会影响中药复方缓释制剂复杂成分的均衡释放;不同处方用量的改良桃胶,会影响药物的释放时间,但不影响其均衡释放.     

Neuroprotection of N-benzylcinnamide on scopolamine-induced cholinergic dysfunction in human SH-SY5Y neuroblastoma cells

Alzheimer's disease, a progressive neurodegenerative disease, affects learning and memory resulting from cholinergic dysfunction. Scopolamine has been employed to induce Alzheimer's disease-like pathology in vivo and in vitro through alteration of cholinergic system. N-benzylcinnamide(PT-3), purified from Piper submultinerve, has been shown to exhibit neuroprotective properties against amyloid-β-induced neuronal toxicity in rat cortical primary cell culture and to improve spatial learning and memory of aged rats through alleviating oxidative stress. We proposed a hypothesis that PT3 has a neuroprotective effect against scopolamine-induced cholinergic dysfunction. PT-3(125–200 n M) pretreatment was performed in human neuroblastoma SH-SY5 Y cell line following scopolamine induction. PT-3(125–200 n M) inhibited scopolamine(2 m M)-induced generation of reactive oxygen species, cellular apoptosis, upregulation of acetylcholinesterase activity, downregulation of choline acetyltransferase level, and activation of p38 and JNK signalling pathways. These findings revealed the underlying mechanisms of scopolamine-induced Alzheimer's disease-like cellular dysfunctions, which provide evidence for developing drugs for the treatment of this debilitating disease.     

HPLC法测定天仙子东莨菪碱和莨菪碱的含量

目的建立天仙子药材中东莨菪碱和莨菪碱的高效液相测定方法。方法采用Symmetrix ODS-H色谱柱,以乙腈-0.1%三氟乙酸水(14∶86)为流动相,检测波长210nm,流速1.0mL/min,测定天仙子药材中东莨菪碱和莨菪碱的含量。结果氢溴酸东莨菪碱和硫酸阿托品的线性范围分别为4.02~513.64μg/mL(r=0.999 9)和4.00~512.00μg/mL(r=0.999 8),平均回收率分别为98.41%和98.79%。结论 HPLC法测定准确、可控,能快速、简便地控制天仙子药材的质量。     

The Usefulness of Head-Up Tilt Testing and Hemodynamic Investigations in the Workup of Syncope of Unknown Origin

To enhance the clinical evaluation of patients suffering from recurrent syncope of unknown origin, the integrity of mechanisms controlling blood pressure was examined in 151 patients utilizing a screening tilt test. Ninety-eight patients had an abnormal blood pressure and/or heart rate response to tilt testing, including provoked syncopal attacks in 63 patients. Whenever indicated, the screening tilt test was followed by blood volume and hemodynamic determinations, as well as autonomic nervous system testing to identify contributing pathophysiological abnormalities (hypovolemia, venous pooling, autonomic dysfunction). Detailed analysis of this battery of tests allowed us to conclude that: (1) The tilt test is commonly a provocative tool in the workup of patients with recurrent syncope due to vasovagal - vasodepressor reactions and other abnormalities of blood pressure regulation; (2) Its usefulness is augmented by associated hemodynamic and blood volume evaluations; (3) The identification of contributory pathophysiological mechanisms of blood pressure control facilitates specific therapeutic interventions.     

内毒素致家兔急性肺损伤时肺和肺外脏器的病理组织学变化及东莨菪碱和前列腺素E_1的保护作用

目的：了解内毒素血症时各脏器受损的病理组织学变化及东莨菪碱和前列腺素Ｅ１的保护作用。方法：大耳白兔５０只，随机分为５组：Ａ组为对照组；Ｂ组为内毒素致伤组（７００μｇ／ｋｇ）；Ｃ组、Ｄ组分别为内毒素致伤后东莨菪碱和前列腺素Ｅ１治疗组，Ｅ组为东莨菪碱和前列腺素Ｅ１联合治疗组。实验前及实验后０．５、２、４和６小时分别测血压和呼吸频率；实验后６．５小时放血处死动物，测肺毛细血管通透指数，同时取肺、心、脑、肝、肾、肾上腺和脾组织作光镜及电镜检查。结果：Ｂ组动物全部于实验后０．５小时出现休克和呼吸困难；６．５小时测得的肺毛细血管通透指数显著高于对照组，各脏器的病理组织学改变以肺最为明显且严重。各治疗组肺受损均轻于Ｂ组，其它脏器在实验后６．５小时的病理变化不明显。结论：内毒素休克时，肺是敏感且最早受损的脏器；东莨菪碱和前列腺素Ｅ１联合治疗组的疗效基本与两药单独治疗组相同。     

Comparison of gastric peristalsis inhibition by scopolamine butylbromide and glucagon: evaluation by electrogastrography and analysis of heart rate variability

Background. Activation of glucagon receptors of the smooth muscle membrane suppresses gastric peristalsis. We evaluated autonomic nervous activity by two methods, electrogastrography (EGG) and analysis of heart rate variability, to compare the inhibiting effects of glucagon and scopolamine butylbromide on gastric peristalsis. Methods. Heart rate variability, EGG, and blood catecholamine levels were measured before and after administration of glucagon (G group), scopolamine butylbromide (SB group), or physiological saline (C group). Autonomic nervous function was evaluated using spectral analysis of heart rate variability, and low frequency (LF) and high frequency (HF) power; the LF/HF ratios were also determined. Results. After administration of scopolamine butylbromide, HF power, an index of parasympathetic nervous activity, decreased; and the LF/HF ratio, an index of sympathetic nervous activity, increased. In contrast, no significant change was observed in autonomic nervous activity after administration of glucagon. The peak power amplitudes of the EGG decreased significantly in the G and SB groups after intramuscular injection, but the difference between the groups was not significant. Furthermore, the dominant frequency increased significantly in the G and SB groups after injection. Serum catecholamine levels showed no significant changes after administration of scopolamine butylbromide or glucagon. Conclusions. Inhibition of gastric peristalsis by glucagon via glucagon receptors on smooth muscles did not influence autonomic nervous activity, unlike the results obtained after administration of scopolamine butylbromide. Therefore, glucagon may be safe for use with elderly patients and those with cardiopulmonary complications.     

Anisocoria from transdermal scopolamine

A transdermal scopolamine patch is an effective medication for relieving motion sickness, treating nausea and vomiting from chemotherapy and decreasing withdrawal side-effects from wearing off opioids. A 14-year-old boy with chronic granulomatous disease and severe infection was admitted to the hospital because of left shoulder aspergillus' infection and pain. The patient required high dose opioid to control the shoulder pain. A unilateral fixed and dilated pupil was noted. We assumed this to be related to the advancing central nervous system aspergillosis. After extensive neurological 'work up', we realized that the anisocoria was related to the transdermal scopolamine patch that we had prescribed for weaning off the opioid.