粒细胞白血病患者环核苷酸代谢的研究

通过对２１例粒细胞白血病患者血浆环－磷酸腺苷（ｃＡＭＰ）含量、腺苷酸环化酶（ＡＣ）、环腺苷酸磷酸二酯酶（ＰＤＥ）比活性和环－磷酸鸟苷（ｃＧＭＰ）含量进行检测，并与１８例非白血病患者和２２例正常人血浆ｃＡＭＰ、ｃＧＭＰ含量和ＡＣ、ＰＤＥ比活力进行比较，发现急性和慢性粒细胞性白血病组的ｃＡＭＰ水平显著低于正常对照组（Ｐ〈０．０１）、ＡＣ比活力也显著低于正常对照组（Ｐ〈０．０１）、ｃＧＭＰ水平显著高于正     

过敏性紫癜患者血浆GMP－140、cAMP、cGMP、IgG和IgA水平的研究

采用放射免疫法（ＧＭＰ－１４０用单位点免疫放射法）测定过敏性紫癜患者治疗前（ｎ＝２１）后（ｎ＝１９）血浆α－颗粒膜蛋白（ＧＭＰ－１４０）、环磷酸腺苷（ｃＡＭＰ）、环磷酸鸟苷（ｃＧＭＰ）、免疫球蛋白Ｇ和Ａ（ＩｇＧ、ＩｇＡ）含量，以３１例健康人作对照．结果，患者与对照比较，血浆ＧＭＰ－１４０（７５４±１６８分子数／血小板，Ｔ＝２．２９５，Ｐ＜０．０５），ｃＡＭＰ（１９．８９±７．９２对１４．２６±５．６３ｎｍｏｌ／Ｌ，Ｔ＝２．９９９，Ｐ＜０．０１），ｃＧＭＰ（４．８７±２．６２对３．４１±１．６９ｎｍｏｌ／Ｌ，Ｔ＝２．４４６，Ｐ＜０．０５），ＩｇＧ（１５．７５±５．５４对１１．４５±４．８６ｇ／Ｌ，Ｔ＝２．９５８，Ｐ＜０．０１）和ＩｇＡ（１．６８±０．８７对１．１６±０．５２ｇ／Ｌ，Ｔ＝２．６９８，Ｐ＜０．０１），且ｃＡＭＰ和ｃＧＭＰ水平升高呈正相关（ｒ＝０．４６９，Ｐ＜０．０５）。过敏性紫癜患者临床治愈后上述物质血浆含量下降，与对照比较无差异（Ｐ＞０．０５）．提示过敏性紫癜患者血浆ＧＭＰ－１４０、ｃＡＭＰ、ｃＧＭＰ、ＩｇＧ和ＩｇＡ可明显升高，临床治愈后恢复正常。     

缺氧时肺动脉内皮细胞与肺动脉平滑肌细胞相互作用对细胞内环核苷酸的影响

目的：观察了培养的小牛肺动脉内皮细胞（ＰＡＥＣ）和肺动脉平滑肌细胞（ＰＡＳＭ）于缺氧时对细胞内环核苷酸的影响。结果：ＰＡＥＣ和ＰＡＳＭ共培养２４ｈ，ＰＡＥＣ细胞内ｃＡＭＰ含量显著降低（Ｐ＜００１），而ＰＡＳＭ细胞内ｃＡＭＰ含量显著增加（Ｐ＜００１），二种细胞内ｃＧＭＰ含量均显著降低（Ｐ＜００１）。缺氧对二种细胞内ｃＡＭＰ含量无显著影响，但能增加ＰＡＳＭ的ｃＧＭＰ含量（Ｐ＜００１），降低ＰＡＥＣ的ｃＧＭＰ含量（Ｐ＜００１）。ＮＯ合酶抑制剂硝基精氨酸对二种细胞的ｃＡＭＰ含量均无显著影响，但能使常氧培养的ＰＡＥＣ和缺氧培养的ＰＡＳＭ细胞内的ｃＧＭＰ含量显著降低（Ｐ＜００１）。结论：ＰＡＥＣ和ＰＡＳＭ的相互作用可引起第二信使系统传递的变化；缺氧可抑制ＰＡＥＣ的ＮＯ合酶活性而诱导ＰＡＳＭ的ＮＯ合酶活性     

急性脑梗塞患者血浆内皮素与血小板内钙含量和聚集关系的探讨

本文用放射免疫分析测定了１６例急性脑梗塞病人的血浆内皮素，用比浊法测定了血小板聚集，用Ｆｕｒａ－２／ＡＭ荧光技术测定了血小板内游离Ｃａ＾２＋含量。急性脑梗塞病人血浆内皮素明显升高（Ｐ〈０．０１），血小板聚集率增设增高（Ｐ〈０．０１），血小板内Ｃａ２＾＋含量增高（Ｐ〈０．０１），且观察到ＡＤＰ诱导的血小板聚集与血小板内Ｃａ＾２＋含量之间呈正相关（ｒ＝０．７８，Ｐ〈０．０１），而血浆内皮素与血小反聚集     

缺氧时肺动脉内皮细胞与肺动脉平滑肌细胞相互作用对细胞内 …

目的：观察了培养的小牛肺动脉内皮细胞（ＰＡＥＣ）和肺动脉平滑肌细胞（ＰＡＳＭ）于缺氧时对细胞内环核苷酸的影响。结果：ＰＡＥＣ和ＵＰＡＳＭ共培养２４ｈ，ＰＡＥＣ细胞内ｃＡＭＰ含量显著降低（Ｐ〈０．０１），而ＰＡＳＭ细胞内ｃＡＭＰ含量显著增加（Ｐ〈０．０１），二种细胞内ｃＧＭＰ含量显著增加（Ｐ〈０．０１）。缺氧对二种细胞内ｃＧＭＰ含量无显著影响，但能增加ＰＡＳＭ的ｃＧＭＰ含量（Ｐ〈０．０１），降低ＰＡ     

荷人鼻咽癌裸鼠血浆MDA,cAMP／cGMP水平及PSP的影响

本实验利用ＢＡＬＢ／Ｃ裸小鼠，复制荷人鼻咽癌裸鼠模型，检测荷瘤鼠血浆丙二醛，ｃＡＭＰ，ｃＧＭＰ和ｃＡＭＰ／ｃＧＭＰ比值，观察云芝糖肽对荷人ＮＰＣ裸鼠的抑瘤作用及对荷瘤鼠血浆ＭＤＡ和ｃＡＭＰ／ｃＧＭＰ等的影响。结果发现荷瘤鼠血浆ＭＤＡ升高，ｃＡＭＰ，ｃＧＭＰ降低，ｃＡＭＰ／ｃＧＭＰ比值升高，高你低浓度ＰＳＰ对荷人ＮＰＣ裸鼠均有明显抗癌作用（Ｐ＜０．０１），抑瘤率５９．５８－９５．５３％；并可降低荷瘤     

精—甘—天冬—丝氨酸肽抑制血小板活化的胞内信号转导机制

本工作在凝血酶活化的大鼠血小板上,观察ＲＧＤＳ肽对血小板聚集,蛋白磷酸化及丝裂素活化蛋白激酶（ＭＡＰＫ）活性的影响,结果发现,ＩＵ／ｍＬ凝血酶明显引起血小板聚集,９５和６６ｋＤ蛋白磷酸化及ＭＡＰＫ活性的增加,应用５０、１００、２００μｍｏｌ／ＬＲＧＤＳ肽共向孵育,呈浓度依赖地抑制凝血酶引起的血小板聚集和ＭＡＰＫ活性,且两者呈正相关（ｒ＝０．８１,Ｐ＜０．０１）。ＲＧＤＳ肽亦呈浓度依赖地抑制凝血酶诱导的９５和６６ＫＤ蛋白磷酸化,与其抑制ＭＡＰＫ活性呈明显正相关（ｒ＝０．４１,Ｐ＜０．０５和ｄ．５３,Ｐ＜０．０１）。提示,ＭＡＰＫ系统参与了凝血酶引起的Ｗ小板聚集,ＲＧＤＳ肽抑制血小板聚集机理之一可能是通过干预血小板内信号传导途径所致。     

PJ－CW对小鼠脾淋巴细胞内环核苷酸含量的影响

济南假单胞菌细胞壁组分（ＰＪ－ＣＷ）是由我院药物所研制的新型微生物制剂。本文就ＰＪ－ＣＷ对小鼠脾细胞总数及脾淋巴细胞内环核苷酸含量的影响作了动态观察。结果显示：小鼠腹腔注射ＰＪ－ＣＷ后，脾细胞总数在第２～６ｄ明显增多，第８ｄ恢复至对照组水平，脾淋巴细胞内的ｃＡＭＰ含量只在第６ｄ出现短暂下降。ｃＧＭＰ含量在第４～６ｄ明显升高（Ｐ＜０．０５）．ｃＡＭＰ／ｃＧＭＰ比值也只在第６ｄ明显降低（Ｐ＜０．０１）。提示：细胞内ｃＧＭＰ含量升高，ｃＡＭＰ／ｃＧＭＰ比值下降可能导致了细胞分裂过程的启动，增强了脾淋巴细胞的功能。     

黄芪多糖、人参茎叶皂甙对创伤小鼠血浆及免疫细胞内cAMP、cGMP的影响

本实验利用小鼠闭合性创伤模型，观察创伤后第４天小鼠血浆、免疫细胞内ｃＡＭＰ、ｃＧＭＰ含量的变化及黄芪多糖（ＡＰＳ）、人参茎叶皂甙（ＧＳ）的调节作用。结果显示：创伤后小鼠血浆内ｃＡＭＰ水平增高，ｃＧＭＰ水平下降，ＣＡＭＰ／ｃＧＭＰ比值升高。腹腔巨噬细胞及脾细胞、胸腺细胞、肠系膜淋巴结细胞在静息状态和激活状态时的ｃＡＭＰ、ｃＧＭＰ含量也显示相似的改变。ＡＰＳ（２５０ｍｇ／ｋｇ）、ＧＳ（５０ｍｇ／ｋｇ）体内应用（每天一次，连续４天）可明显降低创伤小鼠血浆及免疫细胞内ｃＡＭＰ水平，升高其ｃＧＭＰ水平。一定浓度范围内的ＡＰＳ（５０～２５０μｇ／ｍｌ）、ＧＳ（１．０～１００μｇ／ｍｌ）在体外可明显拮抗创伤小鼠激活状态的巨噬细胞及脾细胞内ｃＡＭＰ／ｃＧＭＰ比值的增高。提示：ＡＰＳ，ＧＳ可纠正创伤小鼠血浆及免疫细胞内ｃＡＭＰ、ｃＧＭＰ的比例失衡。     

冠心病患者SOD活性和血小板聚集性及心功能的相关性

为了解自由基在冠心病中的作用，观察了５０例冠心病患者血清ＳＯＤ活性的变化。结果显示心绞痛组患者ＳＯＤ活性显著下降，而ＭＤＡ含量明显升高，二者呈显著负相关，伴血小板聚集性增强和血小板聚集性各项指标呈显著负相关（分别为ｒ＝－０．５２，Ｐ＜０７．０１；ｒ＝－０／４１，Ｐ＜０．０５；ｒ＝－０．４０，Ｐ＜０．０５）．该组患者每搏输出量（ＳＶ）负相相关（分别ｒ＝－０．５２，Ｐ＜０．０１；ｒ＝－０４１，Ｐ＜０．     

炎症渗出液量与其中cAMP,cGMP浓度的关系以及电针刺激的影响

本文以鹿角菜素诱发大鼠胸膜炎动物模型,观察了炎症过程中渗出液的量、渗出液中cAMP和cGMP浓度,以及电针刺激的抗渗出作用与cAMP和cGMP浓度之间的联系。实验结果表明,在致炎后12至24小时内,随着炎症渗出液量的增加,而cAMP浓度下降,cGMP浓度却上升。电针组炎症渗出液量明显少于对照组(P<0.05),cAMP浓度明显高于对照组(P<0.01),cGMP浓度明显低于对照组(P<0.05)。     

慢性肾衰患者血液透析前后血浆心钠素和环核苷酸水平的变化

心钠素和环核苷酸水平的变化对于肾脏的基础和临床研究具有十分重要的意义。为了进一步观察心钠素和环核苷酸水平在肾功能不全发病中的作用,本文对34例CRF病人血液透析前后血浆ANF、cAMP、cGMP水平进行分析。结果显示,CRF患者透析前血浆ANF、cAMP、cGMP含量均显著高于健康人(p<0.001),cAMP/cGMP比值则显著低于健康人(p<0.01)。而经过血透后ANF、cAMP,cGMP含量又明显下降(p<0.001),提示CRF的发病机理与ANF、cAMP、cGMP水平的改变有密切的关系。同时初步分析了这些变化的原因及意义。因此,我们认为测量血浆ANF、cAMP、cGMP水平的变化,对CRF患者的诊治有一定的指导意义。     

柚皮素通过环核苷酸通路拮抗血小板聚集的体外研究

目的:探讨柚皮素拮抗二磷酸腺苷(ADP)诱导血小板聚集的作用机制。方法:采用ELISA检测柚皮素对ADP诱导的大鼠血小板内环磷酸腺苷(cAMP)、环磷酸鸟苷(cGMP)水平的影响。采用高效液相法检测柚皮素对血小板磷酸二酯酶(PDE)活性影响。采用Western blot检测柚皮素对ADP刺激的血小板内血管扩张刺激磷蛋白(VASP)磷酸化形式p-VASP(Ser157)、p-VASP(Ser239)的蛋白水平的影响。分别给予蛋白激酶A(PKA)抑制剂H89、蛋白激酶G(PKG)抑制剂Rp-8-Br-PET-cGMPS和蛋白激酶C(PKC)抑制剂GF109203X预先孵育血小板后,再用柚皮素处理,然后给予ADP刺激,Western blot检测p-VASP(Ser239)蛋白水平。采用血小板聚集仪进一步观察PKA抑制剂、PKG抑制剂预先孵育血小板是否影响柚皮素对ADP诱导血小板聚集的抑制作用。结果:柚皮素剂量依赖性地升高ADP抑制的血小板内cGMP水平,而并不改变cAMP水平。柚皮素还能显著升高血小板PDE活性。Western blot结果显示,柚皮素可明显升高由ADP抑制的p-VASP(Ser239)水平,但不影响p-VASP(Ser157)的蛋白水平,预先孵育PKG或PKC抑制剂并不影响柚皮素对p-VASP(Ser239)蛋白表达的作用,而预先孵育PKA抑制剂后,则能抑制柚皮素对p-VASP(Ser239)蛋白表达的作用。PKA抑制剂能阻断柚皮素对血小板聚集的拮抗作用,而PKG抑制剂并不影响其作用。结论:柚皮素可能通过升高血小板内cGMP水平和激活PKA依赖的信号通路来介导VASP的磷酸化,从而发挥抗血小板聚集的作用。     

葆春方对老年大鼠器官及脑组织中环核苷酸含量的影响

本文采用放射免疫分析，对老年大鼠、青年大鼠，灌以荷春方后的心、肝、肺、脾、肾和脑组织中ｃＡＭＰ和ｃＧＭＰ含量进行测定。结果如下：１）用药组老年大鼠的心、肝、肺组织中ｃＡＭＰ含量降低，而肾和脑中者则升高；２）用药组老年大鼠的肝、肺、脾组织中ｃＧＭＰ含量降低，而心、肾、脑中者含量则升高，使老年大鼠五脏及脑组织中的ｃＡＭＰ、ｃＧＭＰ含量及ｃＡＭＰ／ｃＧＭＰ比值都接近青年对照组。由此可见葆春方可通过改变老     

In vitro cyclic nucleotide responsiveness of leukocytes and platelets in patients suffering from atopic dermatitis

Peripheral blood leukocytes from patients with severe atopic dermatitis (serum IgE levels between 1,560 and 28,000 U/ml) showed a significantly weaker increase in intracellular cAMP after stimulation with epinephrine (10(-5)-10(-3) M) than leukocytes from normals. At the same time stimulation with methylcholine (10(-10)-(10(-4) M) induced a significantly higher increase in intracellular levels of cGMP in the atopic group compared to normals. The immunomodulating agent levamisole induced a slight increase in cAMP and cGMP response both in leukocytes from atopic patients and in normals. Platelet cAMP concentrations were lowered by epinephrine stimulation both in atopics and controls. There was no effect of methylcholine upon platelet cyclic nucleotide levels in the dose range examined. The data support the concept that abnormal cyclic nucleotide responsiveness--not only as beta-adrenergic blockade but also as cholinergic hyperreactivity--may plays a role in the pathogenesis of atopic dermatitis.     

钙离子浓度变化对大鼠缺血心室致颤阈值的影响及其与cAMP、cGMP及ATP的关系

本文目的是观察不同钙离子浓度([Ca~(2 )])对急性局部缺血大鼠心脏室颤阈(VFT)的影响及其与心肌cAMP、cGMP和ATP含量变化的关系。结果表明,[Ca~(2 )]与缺血心脏VFT下降幅度呈正相关(r=0.7998,p<0.05);而[Ca~(2 )]与缺血心肌cAMP/cGMP比值、ATP含量则呈负相关(分别r=-0.887、r=-0.864,均p<0.05);缺血心脏VFT下降幅度与cAMP/cGMP比值亦呈显著负相关(r=-0.992,p<0.01),提示心肌细胞内游离Ca~(2 )水平可能是缺血心室易颤性(VV)的决定因素;cAMP水平或cAMP/cGMP比值则可能是通过影响Ca~(2 )内流而起作用的间接因素;而ATP贮量对缺血心脏VFT下降可能有一定保护作用。     

Platelet aggregation in atopic and normal patients

Platelet aggregation was used as a model to evaluate the proposed beta blockade in subjects with allergic rhinitis and asthma. Studies using epinephrine, adenosine diphosphate (ADP), and streptococcal M protein as aggregating agents showed that there was no significant difference in platelet aggregation between atopics and controls. Furthermore, aggregation induced by all three agents was inhibited by propranolol and phentolamine, as well as by caffeine and dibutyryl cyclic adenosine monophosphate (AMP). This inhibition was evidenced with platelets from both atopics and controls. The results suggest that with platelet aggregation the atopic population taken as a whole does not differ from the normal population. Although certain atopic subjects exhibit unique aggregation patterns, pharmacologic manipulation of this system fails to document that these unique patterns are due to beta blockade.     

连代低氧培养肺动脉平滑肌及内皮细胞的急性低氧反应中环核苷酸的作用

目的:探讨环核苷酸在慢性低氧动物的低氧性肺血管收缩反应(HPV)弱化机制中的作用。方法:用RIA法测定连代常氧与连代低氧培养猪肺动脉平滑肌细胞(PASMC)和内皮细胞(PAEC)的cAMP和cGMP及其在急性低氧时的变化;用图像分析系统检测常氧与低氧培养PASMC在急性低氧时的收缩程度。结果:低氧组PASMC的cAMP、cGMP和PAEC的cGMP基础值较常氧组低(P＜0.01)。急性低氧状态下,低氧组PASMC的cAMP、cGMP含量升高(P＜0.01);低氧组弱收缩反应PASMC的百分率明显高于常氧组。结论:慢性低氧PASMC和PAEC的cAMP、cGMP基础值下降可能与慢性低氧动物肺动脉基础张力增高有关;慢性低氧PASMC在急性低氧反应时cAMP、cGMP含量升高可能是慢性低氧机体HPV弱化的机制之一。     

Platelet thrombopathy in asthmatic patients with elevated immunoglobulin E

Abnormalities of second-wave platelet aggregation were demonstrated in 17 of 33 asthmatic patients in whom drug and diet intake were controlled in the hospital. Mean abnormal responses were significantly greater after epinephrine- (p < 0.001), adenosine diphosphate-(<0.001), collagen- (p = 0.01), and thrombin- (p < 0.001) induced platelet aggregation in patients with immunologically mediated asthma and serum IgE levels >250 U/ml as compared to patients without immunologic factors and/or normal controls. Mean pollen-specific radioallergosorbent (RAST) binding was also significantly higher in patients with abnormal aggregation as compared to normal platelet responders (p = 0.02). Release of serotonin generally reflected abnormal aggregation patterns in asthmatic patients. Platelet factor 4 release was significantly decreased in the same groups of patients. These results suggest that the allergic state may affect platelet membrane responsiveness to multiple aggregating agents.     

Platelet function and structure in myeloproliferative disease, myelodysplastic syndrome, and secondary thrombocytosis

Platelet function and morphologic characteristics were evaluated in 43 patients with myeloproliferative disease (MPD), 5 patients with myelodysplastic syndrome (MDS), and 7 patients with secondary thrombocytosis (ST). Platelet Factor IV (PF4) and B-thromboglobulin (BTG) showed slight elevation in ST but significant elevation in all MPDs. They were either normal or slightly elevated in MDS. Defective platelet aggregation with one or more inducers was seen in 62% of all patients. An epinephrine-induced defect was the most consistent aggregation abnormality. Hyperaggregation and spontaneous aggregation were seen in 15% of patients. Of the eight patients who showed increased bleeding tendency, all eight showed defective aggregation with two or more inducers, five showed decreased surface activation response, as well as decreased or abnormal granules and dense tubular disarray in the transmission electron microscope (TEM) study. Seven patients had clinical evidence of recurrent arterial and venous thromboses. Five of these patients showed hyperaggregation response to adenosine diphosphate and collagen and abnormal Wu and Hoak platelet aggregate ratio. Four patients showed spontaneous aggregation on aggregometer. Surface activation response was significantly increased in five patients, and an increase in platelet granules by TEM study was seen in four patients. Primary thrombocythemia could be differentiated from secondary thrombocytosis (ST) by the presence of abnormal aggregation response and significantly increased PF4 and BTG in the former, and greatly elevated plasma fibrinogen and Factor VIII, as part of acute phase reactant response, in the latter.