马钱子碱和马钱子碱氮氧化物抗血小板聚集及抗血栓形成作用的研究

观察了马钱子碱（Ｂ）和马钱子碱氮氧化物（ＢＮＯ）抗血小板聚集和血栓形成的作用，发现了Ｂ和ＢＮＯ都能显著地抑制由ＡＤＰ和胶原诱导的血小板聚集。与阿斯匹林（ＡＳＰ）比较，在同样终浓度下ＢＮＯ对ＡＤＰ诱导的血小板聚集的抑制作用与ＡＳＰ相似，但对胶原诱导的血小板聚集的抑制作用则强于ＡＳＰ。Ｂ对ＡＤＰ或胶原诱导的血小板的抑制作用均强于ＢＮＯ和ＡＳＰ。Ｂ、ＢＮＯ和ＡＳＰ抗ＡＤＰ诱导的血小板聚集的ＩＤ５０依次为０．８７７，２．３１９和２．０１２ｍｍｏｌ·ｍｌ－１；抗胶原诱导的血小板聚集的ＩＤ５０依次为０．７００，３．９５０，４．１８７ｍｍｏｌ·ｍｌ－１。Ｂ、ＢＮＯ都有类似ＡＳＰ的抗血栓形成作用，血栓抑制率分别为Ｂ：４７．５％、ＢＮＯ：５０．６％和ＡＳＰ：４２．１％。虽然Ｂ的剂量是ＢＮＯ和ＡＳＰ的一半，即有与ＢＮＯ和ＡＳＰ相近的血栓抑制率，但已显示明显的积蓄性毒性。     

大蒜素对血管平滑肌细胞增殖细胞核抗原表达的影响

目的：观察大蒜素对培养的兔主动脉平滑肌细胞（ＳＭＣ）增殖细胞核抗原（ＰＣ－ＮＡ）表达的影响。方法：用免疫组化ＬＳＡＢ法检测ＳＭＣ的ＰＣＮＡ表达，同时测定培养液中超氧化物歧化酶（ＳＯＤ）、脂质过氧化物（ＬＰＯ）、前列环素（ＰＧＩ２）及环磷酸腺苷（ｃＡＭＰ）的含量。结果：大蒜素能增加ＳＯＤ活性，降低ＬＰＯ，升高ＰＧＩ２和ｃＡＭＰ水平，抑制ＳＭＣ的ＰＣＮＡ表达（Ｐ〈０．０５－０．０１）。结论：大蒜素有抑     

花椒油素对血小板聚集的抑制作用

用比浊法测定花椒油素（ＸＴ）对二磷酸腺苷（ＡＤＰ）、花生四烯酸（ＡＡ）和凝血酶诱导的兔血小板聚集的抑制作用。体外实验结果：花椒油素能显著抑制ＡＤＰ、ＡＡ和凝血酶诱导的兔血小板聚集,它们的抑制率分别是２２．４％～７０．１％,１５．３％～６８．２％,２５．８％～７４．６％。体内实验结果：ＸＴ５ｍｇ／ｋｇ给兔灌胃,灌胃后１５ｍｉｎ、３０ｍｉｎ、６０ｍｉｎ和９０ｍｉｎ对ＡＤＰ、ＡＡ和凝血酶诱导的兔血小板聚     

糖尿病大鼠病程不同阶段视网膜组织中内皮素-1水平的变化及意义

目的： 探索糖尿病视网膜病变发生发展的有关因素。方法： 对链脲佐菌素诱导的糖尿病大鼠发病后第４ 、６、１２ 和１６ 周视网膜组织中内皮素１ （ ｅｎｄｏｔｈｅｌｉｎ１ ,ＥＴ１）、环磷酸腺苷（ｃｙｃｌｉｃａｄｅｎｉｎｅ ｍｏｎｏｐｈｏｓｐｈａｔｅ,ｃＡＭＰ） 和环磷酸鸟苷（ｃｙｃｌｉｃｇｕａｎｉｎｅ ｍｏｎｏｐｈｏｓｐｈａｔｅ,ｃＧＭＰ） 的含量进行了检测。结果： 各阶段糖尿病组大鼠视网膜组织中ＥＴ１ 水平明显高于对照组,ｃＡＭＰ含量和ｃＡＭＰ／ｃＧＭＰ比值则明显低于对照组, 随病程延长更为明显,ｃＧＭＰ含量无明显改变。结论：糖尿病视网膜病变的发生和发展可能与高血糖状态下视网膜组织中ＥＴ１ 水平升高所致的视网膜局部微循环功能障碍和代谢紊乱有关。     

黄芪多糖调节创伤小鼠活化T淋巴细胞的分子机制

研究了黄芪多糖（ＡＰＳ）对创伤小鼠活化Ｔ淋巴细胞内白细胞介素＿２（ＩＬ－２）及其受体（ＩＬ－２Ｒ）基因转录表达，ｃＡＭＰ、ｃＧＭＰ含量以及磷脂酰肌醇代谢的调节作用。结果显示：ＡＰＳ对创伤小鼠活化Ｔ淋巴细胞内ＩＬ－２ｍＲＮＡ、ＩＬ－２ＲｍＲＮＡ、ＩＬ－２及ＩＬ－２Ｒ的降低均具有明显的拮抗作用，并可降低创伤小鼠血浆及活化Ｔ淋巴细胞内ｃＡＭＰ含量，增加ｃＧＭＰ含量，提高Ｔ淋巴细胞内三磷酸肌醇（ＩＰ＿３）含量、游离钙Ｃａ￣２）浓度、钙调素（ＣａＭ）、ＣａＭ依赖的蛋白激酶（ＣａＭ－ＰＫ）及蛋白激酶ｃ（ＰＫＣ）的活性。表明ＡＰＳ可通过调节ｃＡＭＰ、ｃＧＭＰ含量以及促进磷脂酰肌醇代谢进而提高创伤后活化Ｔ淋巴细胞内ＩＬ－２及ＩＬ－２Ｒ的基因转录表达。     

2，6-二甲基-4-(3-硝基苯基)-1，4-二氢-3，5-吡啶二羧酸-3-甲酯-5-正戊酯(MN9202)抗实验性血栓形成作用

目的：探讨新的二氢吡啶钙通道阻滞剂ＭＮ９２０２对实验性血栓形成的影响及其作用机制。方法：采用ｉｖ胶原肾上腺素或ｓｃ角叉菜胶，分别复制小鼠肺血栓和尾血栓模型。观察ＭＮ９２０２对实验性肺血栓小鼠死亡率，血栓黑尾形成率及微循环的影响。用凝血酶ＡＤＰ肾上腺素复合诱导剂，复制大鼠脑血栓模型，观察ＭＮ９２０２对大鼠脑血栓损伤的预防作用。结果：ＭＮ９２０２４ｍｇ·ｋｇ－１ｉｐ，能明显降低胶原肾上腺素引起的小鼠死亡率（３０ｖｓ８４Ｐ＜０．０１）；６ｍｇ·ｋｇ－１ｉｇ，对凝血酶诱导的大鼠脑血栓损伤具有保护作用（０．０６９±０．０６８ｖｓ０．１１０±０．０１３，Ｐ＜０．０１）；０．０４，０．４ｍｇ·ｋｇ－１能降低角叉菜胶诱导的血栓黑尾发生率（３０，１０ｖｓ９０，Ｐ＜０．０５；Ｐ＜０．０１），明显减轻微血管内皮的渗出，抑制血小板聚集和ＲＢＣ聚集，改善微血管血流速度。结论：ＭＮ９２０２具有对抗血小板聚集诱导剂及角叉菜胶引起的血栓形成作用。其机制可能与其抑制ＲＢＣ、血小板聚集，保护血管内皮，舒张痉挛血管有关。     

海星甾醇对血小板聚集的药理研究

通过大鼠、大白兔体内、体外血小板聚集实验。评价海星甾醇对大鼠体外实验性血栓形成及经花生四烯酸（ＡＡ）、ＡＤＰ、ＣａＣｌ２诱导血小板聚集的药理作用。海星甾醇ｐｏ４．５、１３．５４０．５ｍｇ／ｋｇ对大鼠体外实验性血栓的抑制率分别为１０．０％、２０．１％、２５．９％（Ｐ〈０．０１）,同时能够抑制经ＡＡ、ＡＤＰ、ＣａＣｌ２诱导的血小板聚集（Ｐ〈０．００１）,提示海星甾醇具有抑制血小板聚集作用。     

糖尿病大鼠病程不同阶段视网膜组织中内皮素—1水平的变化？…

目的：探索糖尿病视网膜病变发和发展的有关因素。方法：对链脲佐菌素诱导的糖尿病大鼠发病后第４、６、１２和１６周视网膜组织中内皮素－１、环磷酸腺苷和环磷酸鸟苷的含量进行了检测。结果：各阶段糖尿病组大鼠视网膜组织中Ｅ１水平明显高于对照组,ｃＡＭＰ含量和ｃＡＭＰ／ｃＧＭＰ比值则明显低于对照组,随病程延长更为明显,ｃＧＭＰ含量无明显改变。结论：糖尿病视网膜病变的发生和发展可能与高血糖状态下视网膜组织中ＥＴ１     

脾虚患者胃粘膜前列腺素和环核苷酸改变的观察

本文观察了７５例慢性胃病患者胃粘膜三种前列腺素和环核苷酸含量，发现脾虚组患者胃粘膜ＰＧＥ＿２、６－ｋｅｔｏ－ＰＧＦ＿（１ａ）、６－ｋｅｔｏ－ＰＧＦ＿（１ａ）／Ｔ×Ｂ＿２比值及ｃＡＭＰ含量均明显低于肝气犯胃组（Ｐ＜０．０５～０．０１），ＴＸＢ＿２、ｃＧＭＰ及ｃＡＭＰ／ｃＧＭＰ比值则两组差异不显著，还发现胃粘膜ＰＧＥ＿２、６－ｋｅｔｏ－ＰＧＦ＿（１ａ）与ｃＡＭＰ呈明显的正相关。提示脾虚时胃粘膜ＰＧ＿ｓ和环核苷酸含量有一定的改变，这些改变可能是脾虚时胃粘膜代谢和功能变化的病理基础。     

穿心莲提取物抗血小板聚集与释放作用及其机理的研究

本研究对６３例心，脑血管疾病患者进行了服药后３ｈ及（或）１周的临床观察，发现穿心莲（ＡＰＮ）对１及５ｍｉｎ血小板聚集率均有明显抑制作用（Ｐ＜０．００１），且随用药时间延长（１周后）疗效更显著。通过２０名志愿者服药前后血浆及血小板５－叛色（５－ＨＴ）测定证明ＡＰＮ能显著抑制血小板释放５－ＨＴ（Ｐ＜０．０１）。透射电镜观察到无论体外加药还是服药后ＡＰＮ均能明显抑制ＡＤＰ诱聚所致的血小板管导系统扩张及颗     

Antiaggregant effects on human platelets of culinary herbs

The inhibitory effects of methanol extracts of 20 herb species on human platelet aggregation were investigated. Allspice, basil, marjoram, tarragon and thyme strongly inhibited the platelet aggregation induced by collagen. Basil, marjoram and tarragon strongly inhibited platelet aggregation induced by ADP. An active compound, arbutin, was isolated from sweet marjoram as an inhibitor of platelet aggregation induced by collagen; ADP, arachidonic acid (AA) and thrombin. Copyright © 1998 John Wiley & Sons, Ltd.     

Human platelet aggregation inhibitors from thyme (Thymus vulgaris L.)

Two antiaggregant compounds, thymol (compound 1) and 3,4,3',4'-tetrahydroxy-5,5'-diisopropyl-2,2'-dimethylbiphenyl (compound 2) were isolated from the leaves of thyme (Thymus vulgaris L.). The structures were determined by (1)H-, (13)C-NMR and mass spectra (MS) studies. These compounds inhibited platelet aggregation induced by collagen, ADP, arachidonic acid (AA) and thrombin except that compound 2 did not inhibit platelet aggregation induced by thrombin.     

芍药苷联合川芎嗪对肌动蛋白微丝诱导血小板活化及血小板凝溶胶蛋白水平的干预效应研究

目的研究肌动蛋白微丝(F-actin)体外刺激对血小板活化及血小板凝溶胶蛋白(gelsolin)浓度的影响,同时观察活血化瘀中药赤芍-川芎有效成分配伍的体外干预效应。方法以人水洗血小板作为研究对象,分为低(2.5μmol/L)、中(5μmol/L)、高(10μmol/L)浓度F-actin组以及花生四烯酸(AA)、二磷酸腺苷(ADP)、凝血酶(thrombin)组,同时设中药F-actin(10μmol/L)组和中药AA组使用芍药苷和川芎嗪联合干预,阿司匹林F-actin(10μmol/L)组和阿司匹林AA组使用阿司匹林作为干预药物,另设对照组。采用流式细胞术检测血小板活化标志物CD62p的表达,使用血小板聚集仪测定最大血小板聚集率(PAR),采用ELISA法测定血小板gelsolin浓度。结果与对照组比较,不同浓度F-actin及AA、ADP、thrombin均可引起PAR和CD62p表达升高(P<0.01),且F-actin呈浓度依赖性。与AA组比较,低、中浓度F-actin组PAR与CD62p表达下降(P<0.01),高浓度F-actin、ADP、thrombin组则无明显差异(P>0.05)。与对照组比较,中、高浓度F-actin组及AA组可诱导血小板gelsolin浓度增高(P<0.05,P<0.01)。与AA组比较,低、中浓度F-actin以及ADP、thrombin组gelsolin浓度下降(P<0.05)。与高浓度F-actin组或AA组比较,川芎嗪和芍药苷与阿司匹林均可抑制F-actin和AA诱导的PAR和CD62p表达升高(P<0.05)。与高浓度F-actin组或AA组比较,川芎嗪和芍药苷可降低F-actin或AA诱导的gelsolin升高(P<0.05),但阿司匹林无此效应(P>0.05)。结论 F-actin体外能够激活血小板导致其聚集、活化,10μmol/L浓度能够诱导血小板大量分泌gelsolin,其效应与AA相似。血小板gelsolin可能是芍药苷和川芎嗪体外抗血小板聚集、活化的一个有效干预靶点。     

Antiplatelet activity of Phellinus baummii methanol extract is mediated by cyclic AMP elevation and inhibition of collagen-activated integrin-α(IIb) β₃ and MAP kinase

Phellinus baumii is a mushroom that has been used as folk medicine against various diseases and is reported to have antidiabetic, anticancer, antioxidant, antiinflammatory and antihypertensive activities. However, information on the effects of P. baumii extract in platelet function is limited. Therefore, the aim of this study was to examine the impact of a P. baumii methanol extract (PBME) on platelet activation and to investigate the mechanism behind its antiplatelet activity. PBME effects on agonist‐induced platelet aggregation, granule secretion, [Ca²⁺]_i mobilization, α_IIbβ₃ activation, cyclic AMP release and mitogen‐activated protein kinase (MAPK) phosphorylations were studied using rat platelets. PBME dose‐dependently inhibited collagen, thrombin and ADP‐induced platelet aggregation with an IC₅₀ of 51.0 ± 2.4, 54.0 ± 2.1 and 53.0 ± 4.3 μg/mL, respectively. Likewise, thrombin‐induced [Ca²⁺]_i and collagen‐activated ATP secretions were suppressed in PBME treated platelets. Aggregation and ATP secretion were also markedly attenuated by PBME alone or in combination with PP2 (Src inhibitor) and U‐73122 (PLC inhibitor) in collagen‐stimulated platelets. Besides, PBME treatment elevated basal cyclic AMP levels and inhibited collagen‐induced integrin‐α_IIbβ₃ activation. Moreover, PBME attenuated extracellular‐signal‐regulated protein kinase 2 (ERK2) and c‐Jun N‐terminal kinase 1 (JNK1) phosphorylations. Further PD98059 (ERK inhibitor) and SP60025 (JNK inhibitor) reduced collagen‐induced platelet aggregation and ATP secretion. In conclusion, the observed PBME antiplatelet activity may be mediated by activation of cyclic AMP and inhibition of ERK2 and JNK1 phosphorylations. Finally, these data suggest that PBME may have therapeutic potential for the treatment of cardiovascular diseases that involve aberrant platelet function. Copyright © 2011 John Wiley & Sons, Ltd.     

羟基红花黄色素A注射剂对家兔血小板聚集、超微结构及血浆GMP-140含量的影响

目的:观察羟基红花黄色素A(HSYA)注射剂对家兔血小板聚集功能及超微结构的影响。方法:采用体内实验法,观察三种剂量的羟基红花黄色素A注射剂(10mg/kg、5mg/kg和2.5mg/kg)对由花生四烯酸(AA,0.35mmol/L)、二磷酸腺苷(ADP,300μmol/L)和血小板活化因子(PAF,3.6nmol/L)诱导的家兔血小板聚集作用的影响,以及血小板超微结构的变化;并单独研究了以PAF为诱导剂的情况下,血浆GMP-140的含量。结果:各剂量HSYA注射剂(10mg/kg、5mg/kg和2.5mg/kg)能抑制AA、PAF诱导的家兔血小板聚集;扫描电镜显示,各剂量HSYA注射剂能减少AA和PAF诱导后的聚集型血小板数量并使树突型血小板突起变少变短;另外,各剂量HSYA注射剂还能降低GMP-140的含量。结论:羟基红花黄色素A注射剂具有显著的抗PAF诱导的血小板聚集作用,抑制血小板的活化,从而为临床抗血小板聚集药物的使用提供更多选择。     

注射用血栓通体外对家兔血小板聚集的影响

目的研究注射用血栓通(冻干,主要成分为三七总皂苷,质量分数为95%)体外对二磷酸腺苷(ADP)、花生四烯酸(AA)、血小板活化因子(PAF)诱导家兔血小板聚集的影响。方法采用Born法,检测ADP、AA、PAF诱导的家兔血小板聚集率。结果与对照组比较,注射用血栓通7.2、14.4 mg/mL组能显著抑制ADP、AA、PAF诱导的兔血小板聚集率(P<0.01),注射用血栓通3.6 mg/mL组能显著抑制ADP诱导的兔血小板聚集率(P<0.01)。结论注射用血栓通具有体外抑制家兔血小板聚集的作用。     

Anti‐platelet Activity of Erythro‐(7S,8R)‐7‐acetoxy‐3,4,3′,5′‐tetramethoxy‐8‐O‐4′‐neolignan from Myristica fragrans

Platelets play a critical role in pathogenesis of cardiovascular disorders and strokes. The inhibition of platelet function is beneficial for the treatment and prevention of these diseases. In this study, we investigated the anti‐platelet activity of erythro‐(7S,8R)‐7‐acetoxy‐3,4,3′,5′‐tetramethoxy‐8‐O‐4′‐neolignan (EATN), a neolignan isolated from Myristica fragrans, using human platelets. EATN preferentially inhibited thrombin‐ and platelet‐activating factor (PAF)‐induced platelet aggregation without affecting platelet damage in a concentration‐dependent manner with IC₅₀ values of 3.2 ± 0.4 and 3.4 ± 0.3 μM, respectively. However, much higher concentrations of EATN were required to inhibit platelet aggregation induced by arachidonic acid. EATN also inhibited thrombin‐induced serotonin and ATP release, and thromboxane B₂ formation in human platelets. Moreover, EATN caused an increase in cyclic AMP (cAMP) levels and attenuated intracellular Ca²⁺ mobilization in thrombin‐activated human platelets. Therefore, we conclude that the inhibitory mechanism of EATN on platelet aggregation may increase cAMP levels and subsequently inhibit intracellular Ca²⁺ mobilization by interfering with a common signaling pathway rather than by directly inhibiting the binding of thrombin or PAF to their receptors. This is the first report of the anti‐platelet activity of EATN isolated from M. fragrans. Copyright © 2013 John Wiley & Sons, Ltd.     

17-甲氧基-7-羟基-苯并呋喃查尔酮对大鼠凝血功能和血小板聚集的影响

目的:研究17-甲氧基-7-羟基-苯并呋喃查尔酮(YLSC)对体内外血小板聚集和凝血功能的影响.方法:将50只SD大鼠随机分为5组:对照组(含0.5％ DMSO的生理盐水),YLSC低、中、高剂量组(2.5,5,10 mg·kg-1),阳性药阿司匹林组(10 mg·kg-1).尾静脉注射相应药物1周后,腹主动脉采血,分别加入二磷酸腺苷(ADP)、胶原和花生四烯酸(AA)诱导血小板聚集,测定大鼠体内外血小板聚集率;同时观察YLSC对大鼠凝血酶原时间(PT)、活化部分凝血激酶时间(APTT)及凝血酶时间(TT)的影响.结果:与对照组相比,YLSC能显著抑制ADP和胶原诱导的大鼠体内、外血小板最大聚集率(P＜0.05或P＜0.01),最大抑制率分别为38.4％,42.5％,对AA诱导的血小板聚集无明显抑制作用;YLSC能显著延长大鼠血浆TT,APTT(与对照组比较,P＜0.05或P＜0.01),对PT无显著影响.结论:YLSC具有对抗血小板聚集和抗凝血作用.     

柠檬醛对大鼠及人血小板聚集作用的影响

柠檬醛是山鸡椒的有效成份之一。研究结果表明:Citral对ADP-Collagen诱导的大鼠血大板聚集有明显的抑制作用(P <0.01),对AA诱导的人外周血血小板聚集也有明显的抑制作用。大鼠口服1g/kg citral也能抑制由AA诱导的血小板聚集。另外,Citral还能抑制血小板聚集时产生的TxA_2样物质的释放。