叶下珠有效部位对血栓形成的影响及其作用机制初探

采用Born方法和改良的Hamburger方法分别测定叶下珠 (Phyllanthusurinaria)含corilagin的有效部位 (代号PUW )在体内外对血小板聚集功能和对血小板与中性粒细胞之间粘附反应的影响 ;应用Myers方法评价PUW灌胃对小鼠尾静脉注射花生四烯酸 (AA)引起猝死的保护作用 ;运用改良的Charl ton方法及陈长勋等方法分别观察PUW灌胃对电刺激大鼠颈动脉血栓形成和下腔静脉血栓形成的影响 ;采用Tomihisa方法 ,观察PUW对大鼠尾尖出血时间的影响。结果显示 ,PUW在体内外对ADP、AA或血小板活化因子 (PAF)诱导的血小板聚集均无明显抑制作用 ;PUW呈浓度依赖性明显阻抑AA激活的血小板与中性粒细胞之间的粘附反应 ,其半数抑制浓度 (IC50 )为 39 7mg/kg。PUW (10、2 0和 4 0mg/kg)灌胃呈剂量依赖性显著减少AA致小鼠死亡的数量 ,明显延长电刺激大鼠颈动脉血栓形成时间 ,减轻大鼠下腔静脉血栓的干、湿重。 2 0mg/kg的PUW对出血时间无明显影响 ,4 0mg/kg的PUW虽延长出血时间 ,但与阿司匹林 (2 0mg/kg)比较 ,出血时间明显缩短 (P <0 0 5 )。本实验结果提示 ,PUW灌胃在多种体内血栓模型中均具有明显的抗血栓形成作用 ,其机制可能与阻抑血小板和中性粒细胞之间的的粘附作用密切相关。     

血管活性药物对冷暴露实验动物肢端皮肤温度的调节作用

目的:在冷暴露实验动物模型上,评价盐酸哌唑嗪(Pra)和消旋山莨菪碱(Ani)对大鼠、小鼠肢端皮肤温度的调节作用。方法:将80只大鼠随机分为8组,室温下灌胃给药,60 min后放入指定温度(5℃、18℃)环境中冷暴露,并于给药后180 min和300 min使用红外摄像仪测定实验动物尾部近心端1/3处的皮肤温度,观察皮肤温度的变化,评价药效。结果:单独使用Pra对大鼠肢端皮肤温度无影响,对小鼠肢端皮肤温度提高效果较差;而单独使用Ani对大鼠和小鼠肢端皮肤温度均无提高作用;两药联用后实验动物尾温得到显著提高,且具有一定剂量依赖性。结论:Pra和Ani联用能有效提高冷暴露大鼠、小鼠的肢端皮肤温度,并且不会降低体心温度。     

冷暴露小鼠尾动脉舒缩功能变化以及血管活性药物的作用特征

目的：研究不同温度条件下血管舒缩功能变化及哌唑嗪、山莨菪碱扩张血管作用变化特征,评价VitE在低温条件下的内皮保护作用,探讨上述药物在冻伤预防过程中的应用前景。方法：利用血管条技术,观察小鼠尾动脉血管在8℃、16℃、25℃、37℃四个温度条件下的收缩及舒张反应特点,比较哌唑嗪、山莨菪碱在不同温度条件下扩血管作用差异。在冷暴露处理的同时预敷Vit E,观察其对低温条件下血管内皮依赖性舒张功能的改善作用。结果：①不同温度条件下苯肾上腺素诱发的血管收缩反应存在明显差异,温度越低,收缩幅度越小;②硝普钠浓度依赖的扩血管作用随着温度的降低明显增强;③与硝普钠作用特点类似,哌唑嗪、山莨菪碱在低温条件下的扩血管作用强于37℃组;④低温能够降低乙酰胆碱内皮依赖的扩血管作用,Vit E能够剂量依赖地对抗低温的影响。结论：随着温度的降低,苯肾上腺素作用下的血管收缩明显减弱,平滑肌靶点扩血管药物的作用显著增强。乙酰胆碱内皮依赖的扩血管作用随温度的下降有所降低,Vit E能够在一定程度上减小低温对乙酰胆碱扩血管作用的影响。     

内皮抑素抗肿瘤血管生成的分子机制

内皮抑素(endostatin)是目前广泛关注的血管生成抑制剂,能特异性地抑制内皮细胞的增殖和迁移,在体内具有良好的抗肿瘤效果。该分子的抗肿瘤作用可能与金属蛋白酶活性、信号通路分子、整合素、原肌球蛋白及黏附受体有关。     

血压昼夜节律特征及其分子调控机制

正常血压具有典型的昼夜节律特征。血压昼夜节律异常与高血压靶器官损害和心血管事件发生呈明显相关关系,是独立于血压水平的重要致病因素。血压昼夜节律的产生和维持与时钟基因的周期性表达有关。时钟基因bmal1、per2是体内生物钟系统运行的关键基因,其表达水平和节律变化直接调节血压的昼夜节律。     

血压昼夜节律特征及其分子调控机制

正常血压具有典型的昼夜节律特征。血压昼夜节律异常与高血压靶器官损害和心血管事件发生呈明显相关关系,是独立于血压水平的重要致病因素。血压昼夜节律的产生和维持与时钟基因的周期性表达有关。时钟基因bmal1、per2是体内生物钟系统运行的关键基因,其表达水平和节律变化直接调节血压的昼夜节律。     

毕赤酵母重组Annexin32的分子特征及其对血凝与血栓形成的影响

采用SDS PAGE、等电聚焦、脱磷酸反应、蛋白质N端氨基酸测序、KPTT及大鼠下腔静脉血栓形成观察 ,发现毕赤酵母重组Annexin32的分子特征较原核产物有了明显变化。有主、次 2条带 ,主带的分子量比原核产物大 ,等电点较理论值低 ,已被磷酸化 ,2条带的N端均携带了来自载体的 4个氨基酸 ,可能对其与活化血小板表面磷脂的结合有所下调 ,导致血凝与血栓形成受到一定的影响 ,但仍具有明显的抗凝及抑制血栓形成作用。     

小鼠体内血栓形成动物模型的建立及在抗血栓药物筛选中的应用

目的 :建立一种无创性小鼠体内血栓动物模型并应用于多种抗血栓药物的药效观察。方法 :用角叉菜胶建立了小鼠体内血栓动物模型。利用此模型观察潘生丁片 ,抗栓胶囊、复方丹参注射液、川芎嗪注射液对血栓形成的影响。结果及结论 :用角叉菜胶建立的小鼠体内血栓动物模型 ,无创伤性 ,操作简易方便。并可应用于多种抗血栓药物的药效观察 ,剂量的选择 ,药物的筛选。     

两种新的抗癌分子

癌症是目前世界上最难征服的疾病之一。最近发现的血管生长抑素（ａｎｇｉｏｓｔａｔｉｎ）和内皮生长抑素（ｅｎｄｏｓｔａｔｉｎ）为人类征服癌症提供了希望。１９９４年,哈佛医学院的Ｆｏｌｋ－ｍａｎ实验室在Ｃｅｌ杂志上报道了一种新的能够抑制血管生长的因子——Ａ...     

小鼠体内血栓形成动物模型的建立及在抗血栓药物筛选中的 …

建立一种无创性小鼠体内血栓动物模型并于多种抗栓药物的药效观察。方法：用角叉菜胶建立了小鼠体内血栓动物模型。利用此模型观察潘生丁片,抗栓胶囊、复方丹参注射液、央求地血栓和的影响。结果及结论：用角叉菜胶建立的小鼠体内血栓动物模型,无创伤性、操作简易方便。并可应用于多种抗血栓药物的药效观察,剂量的选择,药物的筛选。     

Novel protein kinases and molecular mechanisms of autoinhibition

During the past year, crystal structures of the PDK-1, ITK, Aurora-A, c-KIT and FLT-3 protein kinases in complex with several ATP-competitive inhibitors have been determined. Some structures have crystallized in catalytically active conformations, whereas others appear to be in inactive or native conformations. The differences between these two classes of structures provide further understanding of how kinase activity may be self-regulated in the cellular environment and how phosphorylation can modulate signalling at a molecular level. All of these structures provide a basis for designing selective protein kinase inhibitors of use in the treatment of cancer and autoimmune disease.     

玉米副突变及其分子机制

副突变是一种表观遗传现象,通过同源基因间染色质状态信息的转移建立新的基因表达状态,这种表达状态能够通过减数分裂而传递到后代。玉米是研究副突变及其机制的模式植物,目前已经发现有5个基因位点能够发生副突变。对玉米b1副突变系统的广泛研究发现DNA重复序列、siRNA途径、DNA结合蛋白等在副突变状态的建立和维持过程中可能起着重要的作用。     

Unexpected amino acid composition of modern Reptilia and its implications in molecular mechanisms of dinosaur extinction

Dinosaur extinction is a great challenge to evolutionary biology. Although accumulating evidence suggests that an abrupt change of environment, such as a long period of low temperature induced by asteroid hit or other disasters, may be responsible for dinosaur extinction, little is known about the underlying molecular mechanisms. By analyzing the amino acid compositions of 13 biological classes, we found that the charged amino acid content of modern Reptilia, the sibling of dinosaur, is strikingly different from those of other classes, which inspires us to propose a possible molecular mechanism for dinosaur extinction.     

Common cellular and molecular mechanisms in obesity and drug addiction

The hedonic properties of food can stimulate feeding behaviour even when energy requirements have been met, contributing to weight gain and obesity. Similarly, the hedonic effects of drugs of abuse can motivate their excessive intake, culminating in addiction. Common brain substrates regulate the hedonic properties of palatable food and addictive drugs, and recent reports suggest that excessive consumption of food or drugs of abuse induces similar neuroadaptive responses in brain reward circuitries. Here, we review evidence suggesting that obesity and drug addiction may share common molecular, cellular and systems-level mechanisms.     

The ameliorating effects of 2,3-dihydroxy-4-methoxyacetophenone on scopolamine-induced memory impairment in mice and its neuroprotective activity

We isolated 2,3-dihydroxy-4-methoxyacetophenone, a neuroprotective compound from Cynenchum paniculatum in our previous study.The present study was conducted to investigate the possible neuroprotective effect of 2,3-dihydroxy-4-methoxyacetophenone that has been previously isolated from Cynenchum paniculatum on hippocampal neuronal cell line, HT22 cells and its possible cognitive-enhancing effect on scopolamine-induced amnesia in mice.Neuroprotective effect against glutamate-induced neurotoxicity in HT22 cells was evaluated by MTT assay. Also, cognitive enhancing effect against scopolamine (1 mg/kg, ip) induced learning and memory deficit was measured by Morris water maze test. Oral administered of 2,3-dihydroxy-4-methoxyacetophenone (1, 10, 20, 40 and 50 mg/kg) to amnesic mice induced by scopolamine. In Morris water maze test, 2,3-dihydroxy-4-methoxyacetophenone (50 mg/kg) improved the impairment of spatial memory induced by scopolamine. 2,3-Dihydroxy-4-methoxyacetophenone protect HT22 cells on glutamate induced cell-death in a dose-dependent manner (EC₅₀ value: 10.94 μM). Furthermore, 2,3-dihydroxy-4-methoxyacetophenone was found to inhibit [Ca²⁺] accumulation in HT22 cells and had antioxidantive activity. The results showed that 2,3-dihydroxy-4-methoxyacetophenone exert neuroprotective and cognitive-enhancing activities through its antioxidant activity. We suggest that 2,3-dihydroxy-4-methoxyacetophenone improves cognitive function and may be helpful for the treatment of Alzheimer’s disease.     

Biomechanics of haemostasis and thrombosis in health and disease: from the macro‐ to molecular scale

Although the processes of haemostasis and thrombosis have been studied extensively in the past several decades, much of the effort has been spent characterizing the biological and biochemical aspects of clotting. More recently, researchers have discovered that the function and physiology of blood cells and plasma proteins relevant in haematologic processes are mechanically, as well as biologically, regulated. This is not entirely surprising considering the extremely dynamic fluidic environment that these blood components exist in. Other cells in the body such as fibroblasts and endothelial cells have been found to biologically respond to their physical and mechanical environments, affecting aspects of cellular physiology as diverse as cytoskeletal architecture to gene expression to alterations of vital signalling pathways. In the circulation, blood cells and plasma proteins are constantly exposed to forces while they, in turn, also exert forces to regulate clot formation. These mechanical factors lead to biochemical and biomechanical changes on the macro‐ to molecular scale. Likewise, biochemical and biomechanical alterations in the microenvironment can ultimately impact the mechanical regulation of clot formation. The ways in which these factors all balance each other can be the difference between haemostasis and thrombosis. Here, we review how the biomechanics of blood cells intimately interact with the cellular and molecular biology to regulate haemostasis and thrombosis in the context of health and disease from the macro‐ to molecular scale. We will also show how these biomechanical forces in the context of haemostasis and thrombosis have been replicated or measured in vitro.     

Segregation function of the cell and its molecular mechanisms

Current literature on the cell segregation function is reviewed. The modern data on the role of coated pits, coated vesicles and endosomes in receptor-mediated and fluid endocytosis are regarded. Mechanisms of segregation both of inorganic and organic substances in lysosomes are considered. A special attention is paid to the selective accumulation in lysosomes of substances penetrating through plasma membrane. Some modern considerations concerning the role of the ATP-dependent proton pump in maintaining low intralysosomal pH and accumulation of weak bases in lysosomes by means of protonation are given. A great attention is paid to the effect of accumulated foreign substances in lysosomes on lysosomal apparatus functions and some metabolic disorders as consequences of it. The importance of the cell segregation functions and of lysosomotropic compounds for cytopharmacology and cytopathology is emphasized.     

场景的一致性效应及其机制

有关场景一致性效应的研究发现,人们对与背景语义一致的前景物体的命名、分类、搜索和再认等都快于与背景不一致的物体.和与情境一致的物体相比,与情境不一致的物体在中央顶区等部位,会诱发一个幅度更大的负波(N390).旁海马皮层/旁海马位置区(PHC/PPA)和压部后皮层(RSC)是负责场景加工的重要脑区.场景一致性效应的时间进程可能首先由低空间分辨率(LSF)信息激活眶额皮层(OFC)(130 ms左右)、PHC/PPA和RSC,之后LSF信息与高空间分辨率(HSF)信息在颞叶进行整合.在诸多理论模型中,情境促进模型从生理角度对一致性效应作了较充分的解释.