五味子醇甲对Aβ1-42诱导SH-SY5Y细胞的RAGE-ROS-凋亡通路的影响

目的探讨五味子醇甲(Schisandrin,SCH)对Aβ1-42诱导SH-SY5Y的RAGE/ROS/凋亡通路的影响。方法MTT法检测control组、SCH高中低剂量组的细胞活力,探讨SCH高中低剂量组对SH-SY5Y细胞的保护作用。MTT法检测control组、Aβ组、Vitamin E组及SCH高中低剂量组细胞活力、双染法观察细胞凋亡和DHE染色法检测ROS含量,探讨SCH对Aβ1-42诱导的SH-SY5Y的细胞损伤的保护作用。Western-blot法检测control组、Aβ组、SCH组RAGE蛋白,探讨SCH对Aβ1-42诱导SH-SY5Y的RAGE影响。结果与control组比较,SCH各剂量组细胞活力均显著增强(P<0.01)。与Aβ组比较,各给药组细胞活力均明显增强(P<0.01)和细胞凋亡率均明显下降(P<0.01);各给药组检测ROS的荧光强度均减弱(P<0.01),SCH(5.0μg/mL)组RAGE蛋白表达降低,有显著性差异(P<0.05)。结论SCH防治阿尔茨海默病的抗氧化作用机制可能与降低ROS含量、细胞凋亡率和下调RAGE蛋白表达有关。     

The essentiality of Bcl-2, PKC and proteasome-ubiquitin complex activations in the neuroprotective-antiapoptotic action of the anti-Parkinson drug, rasagiline

The anti-Parkinson drug, rasagiline, a irreversible propargyl possessing monoamine oxidase B inhibitor can protect neurons in vitro and in vivo from a variety of neurotoxic insults including SIN-1, glutamate, the parkinsonism inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, N-methyl-(R)-salsolinol and including beta amyloid protein. Recent studies have shown that rasagiline rapidly modulates intracellular signaling pathways involved in cell survival and death. Specifically rasagiline activates Bcl-2, Bcl-xl, protein kinase C (PKC) and reduces Bax in a variety of cells including PC-12 and neuroblastoma human dopamine derived SH-SY5Y cells. These enzymes play key roles in cellular events including modulation of apoptotic processes, neuronal plasticity and amyloid precursor protein processing. This pharmacological action of rasagiline is also associated with the prevention of the neurotoxin induced fall in mitochondrial membrane potential, opening of mitochondria permeability transition pore, activation of proteasome-ubiquitin complex, inhibition of cytochrome c release and prevention of caspase 3 activation, similar to the actions of cyclosporin A or Bcl-2 over expression in SH-SY5Y cells. Rasagiline and its various derivatives induces PKC dependent release of soluble amyloid precursor protein alpha and which is blocked by inhibitors of alpha-secretase, PKC and MAPK-dependent signaling. Structure-activity relationship with various propargyl containing derivatives of rasagiline including propargylamine itself has shown that the above described pharmacological action of these compounds resides in the propargylamine moiety. These results have provided a new understanding into the mechanism of neuroprotective actions of rasagiline and its anti-Alzheimer drug derivatives TV3326 and TV3279, which are relevant for therapy of Parkinson's disease, Alzheimer's disease and other neurodegenerative diseases.     

紫金解毒液活血化瘀实验研究

目的：了解紫金解毒液对动物血液流变学、微循环和静脉血栓形成的影响。方法：采用实验动物制造血瘀模型，观察紫金解毒液对大鼠血液流变学、大鼠肠系膜微循环和大鼠静脉血栓形成的影响。结果：紫金解毒液能明显升高红细胞压积，降低全血粘度，全血还原粘度，血浆粘度，改善血液流变学与对照组比较差异均有统计学意义（P值均〈0．05-0．01）；能抑制肾上腺素所致的缩血管反应，改善微循环；能阻滞由结扎静脉所致的血栓形成，减轻静脉系统瘀血。结论：紫金解毒液具有活血化瘀作用。本品对于血粘度增高、微循环障碍的病人以及血栓栓赛性疾病无疑是有益的。     

Measuring and estimating diagnostic accuracy when there are three ordinal diagnostic groups

This article studies the problem of measuring and estimating the diagnostic accuracy when there are three ordinal diagnostic groups. We use a receiver operating characteristic (ROC) surface to describe the probabilities of correct classifications into three diagnostic groups based on various sets of diagnostic thresholds of a test and propose to use the entire and the partial volume under the surface to measure the diagnostic accuracy. Mathematical properties and probabilistic interpretations of the proposed measure of diagnostic accuracy are discussed. Under the assumption of normal distributions of the diagnostic test from three diagnostic groups, we present the maximum likelihood estimate to the volume under the ROC surface and give the asymptotic variance to the estimate. We further propose several asymptotic confidence interval estimates to the volume under the ROC surface. The performance of these confidence interval estimates is evaluated in terms of attaining the nominal coverage probability based on a simulation study. In addition, we develop a method of sample size determination to achieve an adequate accuracy of the confidence interval estimate. Finally, we demonstrate the proposed methodology by applying it to the clinical diagnosis of early stage Alzheimer's disease based on the neuropsychological database of the Washington University Alzheimer's Disease Research Center.     

炙甘草汤注射液对正常及“阴虚”大鼠心律失常影响的实验研究

“阴虚”大鼠对肾上腺素诱发的心律失常，其心电图显示心率加快、心律不齐及Ｔ波异常。诱发心律失常所用肾上腺素剂量明显低于健康大鼠，心律失常程度亦较健康大鼠严重。静脉注射炙甘草汤注射液０．５ｍｌ／１００ｇ可降低健康和“阴虚”大鼠心律失常的发生率，减轻心律失常程度。尤以对“阴虚”大鼠效果更显著。实验提示，炙甘草汤注射液抗心律失常作用机理，可能涉及其改善植物神经系统功能紊乱，抑制交感神经偏亢等作用。     

补肾通络涤痰方治疗AD模型大鼠的实验研究

目的：探讨补肾通络涤痰方对AD模型大鼠的治疗作用及作用机理。方法：将动物随机分为6组,即假手术组、模型组、复方高中低剂量组,脑复康组,每组8只。采用D-半乳糖诱导建立阿尔茨海默病（AD）动物模型,观察补肾通络涤痰方对AD模型大鼠学习记忆、脑组织SOD活力、MDA和NO含量的影响。结果：与假手术组比较,模型组大鼠学习记忆能力明显减退,脑组织SOD活力、MDA和NO含量均明显降低,复方组学习记忆能力得到明显改善,脑组织SOD活力、MDA和NO含量均明显得到提高。结论：补肾通络涤痰方能明显改善AD模型动物学习记忆,及抗自由基对脑组织的损伤。     

痹痛贴对小鼠耳廓微循环作用的实验研究

目的:研究痹痛贴对小鼠耳廓微循环的影响。方法:将小鼠随机分为对照组,赋形剂组,麝香舒活灵组,痹痛贴低、中、高剂量组,用微循环仪观察正常小鼠给药后10min、30min、60min耳廓微静脉、微动脉管径、血液流速。注射肾上腺素造成耳廓微循环障碍,观察造模后10min、30min、60min小鼠的耳廓微静脉、微动脉管径、血液流速。结果:痹痛贴中、高剂量能不同程度的增强正常小鼠耳廓微静脉、微动脉管径、血液流速,和赋形剂组、空白对照组比较有显著性差异(P<0.01),痹痛贴中、高剂量能改善肾上腺素导致的小鼠耳廓微循环障碍,与赋形剂组、模型对照组比较微静脉、微动脉管径、血液流速水平明显提高(P<0.01)。结论:痹痛贴具有明显的改善微循环的作用。     

含地黄饮子脑脊液对PC-12细胞氧化应激的影响

目的 通过建立Aβ损伤的PC12细胞模型,分析含地黄饮子脑脊液对PC-12细胞氧化应激的影响.方法 将PC12细胞离体培养,待细胞进入对数生长期后吸弃培养液,分别加入空白培养液10％、正常脑脊液10％、含安理申脑脊液10％、含地黄饮子脑脊液5％、含地黄饮子脑脊液10％、含地黄饮子脑脊液20％,并加培养液补至等量,即成为:空白组、模型组、安理申组、地黄饮子低剂量组、地黄饮子中剂量组、地黄饮子高剂量组,37℃孵育2h.除空白组外各组均加入4μl经老化处理终浓度为10μ mol/L的Aβ25-35,建立AD细胞模型,空白组则加入4μl空白培养液,继续37℃孵育24h.然后收集培养液,离心细胞.检测各组PC12细胞培养液中MDA、SOD、CAT、GSH-Px的含量.结果 地黄饮子能降低Aβ25-35损伤PC-12细胞培养液中的MDA含量,提高PC-12细胞培养液中SOD的活性、提高CAT、GSH-Px的含量即抗氧化酶活性,提高自由基清除能力,减少自由基对PC-12细胞的损伤.结论 含地黄饮子脑脊液可能通过改善Aβ25-35损伤的PC-12细胞状态,减轻脂质过氧化反应,提高降低的抗氧化酶活性,清除自由基,从而起到保护细胞的作用.     

New 1H‐Pyrazole‐4‐Carboxamides with Antiplatelet Activity

Nine title compounds were synthesized and investigated in the Born test for their antiplatelet activities against collagen, ADP, adrenaline, and platelet activating factor (PAF) as inducers of the aggregation. Using collagen three compounds with IC₅₀ values below 100 μM were found ( 3b , 3e , 3i ). Activities in nanomolar concentrations were observed against ADP ( 3b , IC₅₀ = 9.4 nM), adrenaline ( 3i , IC₅₀ = 5.8 nM), and platelet activating factor ( 3e , IC₅₀ = 0.45 nM).     

去卵巢大鼠端脑皮质和海马病理改变及氨基胍和补肾方药的防治效应

目的探讨去卵巢大鼠端脑皮质和海马病理改变及氨基胍和补肾方药的防治效应,为阿尔茨海默病防治药物筛选提供参考。方法将36只雌性SD大鼠随机分为假切除组、去卵巢组、氨基胍防治组和补肾方药防治组,各9只。去卵巢组、氨基胍防治组和补肾方药防治组行背部切口切除双侧卵巢,假切除组切除腹腔等体积的脂肪组织。切除卵巢4周后氨基胍防治组饮用1‰盐酸氨基胍水溶液,剂量为盐酸氨基胍50mg/(kg·d);补肾方药防治组予补肾方药灌胃,剂量为生药6.3g/(kg·d);去卵巢组和假切除组予与补肾方药防治组相应容积自来水灌胃。喂养16周后,取脑组织观察端脑皮质和海马的病理改变。结果去卵巢组大鼠端脑皮质及海马组织出现神经元颗粒变性和神经原纤维缠结等,氨基胍防治组和补肾方药防治组神经元的变性现象及神经原纤维缠结明显改善,且在受损区周围有致密的神经纤维网出现。结论去卵巢大鼠可出现阿尔茨海默病样脑病理改变,氨基胍和补肾方药均可防治上述病理改变且促进脑受损区周围致密神经纤维网形成。