滋阴清热治咳喘

咳喘是肺系统病常见的两个病状 ,以咳嗽、略痰、喘息为主要临床表现 ,外感内伤皆可引起。咳有新久寒热之分 ,喘有虚实轻重之别 ,临床上咳喘二症常同时并见。喻嘉言认为“咳者 ,肺之本病也。”《灵枢·胀论》曰“肺胀者 ,虚满而喘咳”。本病常因寒温失调 ,饮食不节 ,怒恐劳倦等     

抗胆碱药对大鼠血浆环核苷酸含量影响

阿托品4、6、10mg/kg ip可显著地降低大鼠血浆cGMP含量(P<0.05);东莨菪碱、B-7601分别需要10.15mg/kg ip。三药对血浆cAMP含量的影响无统计学意义。唯阿托品6.10mg/kg可提高cAMP/cGMP的比值(P<0.05)。结果提示:三药对大鼠血浆cGMP含量的影响,阿托品>东莨菪碱>B-7601。     

环氧氯丙烷染毒大鼠肝和脑干组织中cAMP,cGMP和CaM含量的变化

应用放免技术和钙调泰(CaM)的酶联免疫测试法(ELISA)测定了大鼠EPI染毒后肝和脑干组织中cAMP、cGMP及CaM的含量变化。结果表明,随着染毒剂量的增加肝组织中cAMP、cGMP和CaM含量均呈上升趋势,其中,cAMP和CaM上升一致,cAMP/cGMP值升高;脑干组织中cAMP含量增加,cGMP和CaM无明显变化。本文还讨论了EPI染毒后脑干组织中cAMP、cGMP和DaM含量变化的可能机制和意义。     

环磷腺苷葡胺对儿童哮喘的治疗作用及机制探讨

目的：考察环磷腺苷葡胺对儿童哮喘患者的临床疗效,并初步探讨其机制。方法：选择2007年10月～2008年6月本院收治的哮喘急性期患儿51例,随机分为治疗组（29例）和对照组（22例）,另选24例健康儿童作为正常组。对照组给予糖皮质激素及支气管扩张剂常规治疗,治疗组在常规治疗的基础上静脉点滴环磷腺苷葡胺2.5～5mg/（kg.次）,每日1～2次,连续7d,分别于治疗前后测定各组患儿血浆cAMP、cGMP水平及cAMP/cGMP。结果：哮喘患儿急性期外周血浆cGMP水平高于正常组（P〈0.05）;cAMP,cAMP/cGMP水平低于正常组（P〈0.05）;给予环磷腺苷葡胺治疗的哮喘患儿外周血浆cGMP水平低于常规治疗组（P〈0.05）;cAMP、cAMP/cGMP水平高于常规治疗组（P〈0.05）。结论：环磷腺苷葡胺对哮喘急性期患儿有较好的治疗作用,其机制可能与纠正cAMP/cGMP失衡有关。     

褪黑素对吗啡戒断大鼠脑内cAMP和cGMP含量的影响

目的 :观察褪黑素 (MT)对吗啡戒断大鼠不同脑区cAMP和cGMP含量的影响。方法 :以剂量递增法连续皮下注射吗啡建立吗啡依赖模型 ,采用放射免疫学方法测定脑内cAMP和cGMP的含量。结果 :(1)MT对大鼠吗啡戒断症状具有明显的抑制作用 ;(2 )与对照组比较 ,吗啡依赖大鼠的纹状体、间脑、中脑、脑桥和海马内cAMP含量显著增高 (P <0 0 5 ,P <0 0 1) ,cGMP含量显著下降 (P <0 0 5 ,P <0 0 1)。与吗啡依赖组比较 ,催促戒断大鼠海马和纹状体内cAMP的含量显著升高 (P <0 0 5 ) ,而cGMP含量显著下降 (P <0 0 5 ,P <0 0 1) ,其他部位则无明显变化 ;(3)褪黑素急性治疗可使吗啡戒断大鼠纹状体、间脑、中脑、脑桥和海马内cAMP含量明显下降 (P <0 0 5 ,P <0 0 1) ,cGMP含量明显增高 (P <0 0 5 ,P <0 0 1)。结论 :MT可显著抑制大鼠吗啡戒断反应 ,并与调节中枢cAMP和cGMP含量有关。     

脑桥—延髓中毒蕈碱受体亚型与环核苷酸的关系

研究脑桥－延髓中Ｍ受体亚型与环核苷酸的关系。大鼠ｉｐ药物，脑桥－延髓等组织中ｃＧＭＰ和ｃＡＭＰ含量分别用放射免疫法和竞争性蛋白结合法测定，对照组ｉｐ生理盐水。ｉｐ匹鲁卡品，脑桥－延髓中ｃＧＭＰ含量增加，ｃＡＭＰ变化不明显，ｉｐ哌仓西平或东莨菪碱可拮抗之，ｉｐ６β－乙酰氧基去甲托烷１２μｇｋｇ＾－１，脑桥－延髓中ｃＡＭＰ含量减少，而２５μｇｋｇ＾－１使ｃＡＭＰ和ｃＧＭＰ减少，ｉｐＡＦＤＸ１１６或阿托     

基于AVP-cAMP-AQP_2探讨黄柏及其不同炮制品的滋阴作用

目的研究黄柏及其不同炮制品的滋阴作用。方法以黄柏及其不同炮制品的提取物灌胃,观察大鼠的尿量、尿渗透压的变化,检测大鼠血中皮质醇、cAMP和AVP含量,并对大鼠髓质水通道蛋白2免疫组化。结果黄柏及其不同炮制品均能提高阴虚模型大鼠的尿量,降低尿渗透压;降低阴虚模型大鼠血液中的皮质醇、cAMP和AVP含量;能提高肾阴虚模型大鼠肾脏的APQ2表达。结论黄柏及其炮制品均具有不同程度的滋阴作用。     

龙虎黄芪汤对乙肝患者的cAMP、cGMP、LPO、SOD变化的影响

目的研究龙虎黄芪汤对乙肝患者cAMP、cGMP、LPO、SOD变化的影响。方法采用放射免疫比色法分析。结果服用龙虎黄芪汤后cAMP、SOD含量升高,cAMP／cGMP比值增加,LPO减少。     

人参花皂甙对小鼠心肌cAMP和cGMP含量的影响

给小鼠口服人参花皂甙50mg/kg,25mg/kg和12.5mg/Kg,并设人参根皂甙组,并每天口服该皂甙50mg/kg,连续灌服10天,测得小鼠心肌cAMP和cGMP合量。人参花皂甙的三个剂量组小鼠心肌cAMP含量较生理盐水对照组小鼠心肌cAMP含量均有非常显著的增高(P<0.01),且能较清楚地看出随着药物剂量的增加,cAMP的含量亦增加。人参花皂甙能使小鼠心肌cGMP含量增加,除了12.5mg/kg剂量组外,其余各组经统计学处理,差异非常显著(P<0.01)。人参花皂甙的三个剂量组cAMP/cGMP比值也是随着药物剂量的增加,比值亦增加。     

Effects of Dipyridamole on the Glyceryl–trinitrate–induced Inhibition of Coronary Artery Muscle Tone and Platelet Aggregation in Relation to Cyclic Nucleotide Metabolism

Abstract: The effects of glyceryl–trinitrate (GTN) and dipyridamole (DIP) on relaxation of bovine coronary arteries and on inhibition of aggregation of human platelets have been studied in vitro with special reference to the cyclic GMP (cGMP) system. GTN had a dose–dependent relaxant effect on bovine coronary arteries, and at a high concentration (10^–5 M) it had an inhibiting effect on platelet aggregation. The effects were associated with an increase in the cGMP levels of the tissues. DIP (5 × 10^–7 M respectively 5 × 10^–6 M) potentiated the coronary artery relaxation induced by GTN (10^–8 M) and the inhibition of platelet aggregation caused by GTN in the concentrations 10^–7–10^–4 M. The potentiation was associated with higher levels of cGMP than those produced by GTN alone, at least in bovine coronary arteries. However, at a concentration of 10^–4 M, GTN, in combination with DIP, caused a significant fall in the cGMP level compared to GTN alone. GTN and DIP were not found to significantly increase the cAMP levels in the concentrations tested. DIP was shown to inhibit phosphodiesterase (PDE) from both platelets and bovine coronary arteries. This might be one of the possible mechanisms that can explain the above mentioned potentiation. It is suggested that the combination of DIP+GTN may be of some clinical importance since the potentiating effects were seen at concentrations comparable to the therapeutic plasma concentration for the respective drugs     

Cyclic GMP protein kinase activity is reduced in thyroxine-induced hypertrophic cardiac myocytes

1. We tested the hypothesis that the cGMP-dependent protein kinase has major negative functional effects in cardiac myocytes and that the importance of this pathway is reduced in thyroxine (T4; 0.5 mg/kg per day for 16 days) hypertrophic myocytes. 2. Using isolated ventricular myocytes from control (n = 7) and T4-treated (n = 9) rabbit hypertrophic hearts, myocyte shortening was studied with a video edge detector. Oxygen consumption was measured using O2 electrodes. Protein phosphorylation was measured autoradiographically. 3. Data were collected following treatment with: (i) 8-(4-chlorophenylthio)guanosine-3',5'-monophosphate (PCPT; 10-7 or 10-5 mol/L); (ii) 8-bromo-cAMP (10-5 mol/L) followed by PCPT; (iii) beta-phenyl-1,N2-etheno-8-bromoguanosine-3',5'-monophosphorothioate, SP-isomer (SP; 10-7 or 10-5 mol/L); or (iv) 8-bromo-cAMP (10-5 mol/L) followed by SP. 4. There were no significant differences between groups in baseline percentage shortening (Pcs; 4.9 +/- 0.2 vs 5.6 +/- 0.4% for control and T4 groups, respectively) and maximal rate of shortening (Rs; 64.8 +/- 5.9 vs 79.9 +/- 7.1 micro m/ s for control and T4 groups, respectively). Both SP and PCPT decreased Pcs (-43 vs-21% for control and T4 groups, respectively) and Rs (-36 vs-22% for control and T4 groups, respectively), but the effect was significantly reduced in T4 myocytes. 8-Bromo-cAMP similarly increased Pcs (28 vs 23% for control and T4 groups, respectively) and Rs (20 vs 19% for control and T4 groups, respectively). After 8-bromo-cAMP, SP and PCPT decreased Pcs (-34%) and Rs (-29%) less in the control group. However, the effects of these drugs were not altered in T4 myocytes (Pcs -24%; Rs -22%). Both PCPT and cAMP phosphorylated the same five protein bands. In T4 myocytes, these five bands were enhanced less. 5. We conclude that, in control ventricular myocytes, the cGMP-dependent protein kinase exerted major negative functional effects but, in T4-induced hypertrophic myocytes, the importance of this pathway was reduced and the interaction between cAMP and the cGMP protein kinase was diminished.     

六味地黄汤醇提水洗脱部位对小鼠阴虚模型的影响

目的观察六味地黄汤醇提水洗脱部位对阴虚小鼠体质量、免疫功能、肝组织氧化指标和cAMP、cGMP、T3、T4含量的影响,评价其滋阴作用。方法将小鼠每日灌胃给予甲状腺片(150 mg·kg-1)和利血平(1 mg·kg-1)致阴虚模型,同时给予治疗药物,7 d后检测小鼠体质量增长率、胸腺、脾指数及血浆中cAMP、cGMP、T3、T4,肝匀浆SOD、GSH-Px和MDA等,观察六味地黄汤醇提水洗脱部位对阴虚型小鼠的影响。结果六味地黄汤醇提水洗脱部位能提高阴虚小鼠体质量增长率、胸腺和脾脏指数,降低阴虚小鼠肝组织中SOD和GSH-Px活性,升高MDA含量,降低血清cAMP、T3、T4含量和cAMP/cGMP比值,高剂量组与模型组比较有统计学意义(P<0.05,P<0.01);六味地黄汤亦可改善以上各项指标,但与模型组相比无统计学意义。结论六味地黄汤醇提水洗脱部位具有显著滋阴作用,优于传统六味地黄汤煎剂。     

Cyclic GMP and acid production in isolated gastric cells of the rat

Summary Just as cAMP is regarded as an intracellular mediator of histamine, so has cGMP been connected with cholinergic stimulation of gastric acid secretion. The object of the present investigation was to study the possible role of cellular cGMP on ¹⁴C-aminopyrine uptake, an indirect measure of parietal cell H⁺-production, by using mixtures of isolated rat gastric cells and fractions with different parietal cell content. Cellular cAMP and cGMP. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) enhanced the cAMP and cGMP of gastric cells in a time- and concentration-dependent manner, by 98 and 124% (1 mmol/l) and was included in all further studies. In parietal cell enriched fractions, histamine elevated cAMP by 109% (100 mol/l) without changing cGMP while carbachol did not influence either nucleotide. Various thiols and nitrogen compounds strongly enhanced cellular cGMP, e. g. hydroxylamine and l-cysteine (1 mmol/l) by 527 and 656%, whereas changes in cAMP were minimal. The hydroxylamine response occurred in parietal cell depleted and enriched fractions. ¹⁴ C-aminopyrine (AP) uptake. IBMX alone reduced the basal AP uptake, potentiated the effect of histamine and inhibited the effect of carbachol, which alone stimulated basal accumulation by 302%. The most efficacious stimulant of parietal cell H⁺-production was dibutyryl cAMP (582%, 100 mol/l), whereas dibutyryl cGMP was without effect. However, this latter compound (1 mmol/l) reduced AP accumulation due to dibutyryl cAMP almost completely. Thiols and nitrogen compounds all more or less reduced AP uptake.The data contraindicate the theory of a second messenger function for cGMP in cholinergic acid stimulation of the rat stomach. They show, that an increase in cGMP is associated with low H⁺-production, even if cAMP levels are raised above their resting state. Thus, the results suggest that cGMP rather mediates inhibition of acid secretion, possibly by counteracting the messenger function of cAMP.This study was supported by the Deutsche Forschungsgemeinschaft     

Tamoxifen影响人垂体腺瘤细胞增殖及其机制

目的研究tamoxifen对人垂体腺瘤细胞的增殖代谢和DNA合成的影响,并深入探讨tamoxifen影响垂体腺瘤细胞增殖作用的机制,观察tamoxifen作用后垂体腺瘤细胞周期、细胞内蛋白激酶C(PKC)及cAMP/cGMP的变化。方法采用MTT和[3H]TdR参入实验检测tamoxifen对人垂体腺瘤细胞增殖和DNA合成的影响;用流式细胞技术检测tamoxifen对垂体腺瘤细胞周期的影响;通过PKC活性及cAMP和cGMP含量测定,深入探讨tamoxifen影响垂体腺瘤细胞增殖分化的分子机制。结果①tamoxifen抑制垂体腺瘤细胞的增殖和DNA合成,并呈剂量依赖性;②tamoxifen处理的垂体腺瘤细胞G1期DNA含量升高,S期和G2期DNA含量降低;③与空白处理组相比,使用PKC的激动剂PMA处理培养的人垂体腺瘤细胞时可使胞膜和细胞总PKC活性浓度均升高,但tamoxifen作用15min后,胞浆、胞膜和细胞总PKC活性均下降;④tamoxifen作用于人垂体腺瘤细胞15min后,胞内cAMP水平升高,而cGMP没有明显改变。结论实验结果为探讨tamoxifen抑制垂体腺瘤细胞增殖的分子机制提供了重要线索,同时提示,tamoxifen对垂体腺瘤细胞增殖分化的调控作用是细胞内多信息系统相互整合的结果。     

磷酸二酯酶抑制剂与学习记忆相关信号转导通路研究进展

大量的研究表明,环磷酸腺苷反应元件结合蛋白(cAMP response element binding protein,CREB)直接或间接激活相关基因转录,进而表达c-fos、c-jun、BDNF等,在神经元应激损伤后的再生、存活及修复以及学习记忆等方面发挥重要作用。磷酸二酯酶可以水解环磷酸腺苷(cyclic AMP,cAMP)及环磷酸鸟苷(cyclic GMP,cGMP),进而影响其下游信号转导,发挥对CREB的调节作用。该文从磷酸二酯酶抑制剂与学习记忆相关信号通路的关系及在学习记忆障碍中发挥的作用予以综述,并由该通路入手对发现治疗神经退行性变疾病药物作用新靶点的可能性予以展望。     

温度通过cAMP及cGMP对人淋巴细胞E受体的影响

作者用放射免疫测定及E玫瑰花环测定法检测了不同温度,不同保存时间对淋巴细胞E受体及细胞内cAMP相cGMP的影响,结果表明,随着温度的降低及保存时间的延长,E玫瑰花环的抑制率逐渐增加(P<0.05及0.01)。淋巴细胞内的cAMP含量升高,cGMP含量稍下降,cAMP/cGMP比值增大(P<0.05及0.01)。并对温度、淋巴细胞E受体及环核苷酸三者之间关系进行探讨。     

抗菌药物对氟康唑动态抗真菌作用及透过生物膜的影响

目的：测定试验用抗菌药物与氟康唑联合的动态抗真菌作用,并评价试验用抗菌药物对氟康唑透过生物膜的影响。方法：采用活菌计数法描绘联合用药对白色念珠菌的动态杀菌曲线,以“三明治”透膜实验法评价试验用抗菌药物对氟康唑透过生物膜的影响。结果：试验抗菌药物对氟康唑有不同程度的增效作用,其中米诺环素和利福平对氟康唑透过耐药白色念珠菌生物膜的作用及其对氟康唑动态抗真菌的增效作用最强,氧氟沙星、阿奇霉素等次之。结论：试验用抗菌药物能促进氟康唑透过白色念珠菌生物膜,增强氟康唑的动态抗真菌作用。     

阿魏酸钠防护晶状体上皮细胞氧化损伤的信号转导机制

目的:探讨阿魏酸钠对氧化损伤的晶状体上皮细胞内Ca2 、环磷酸腺苷(cAMP)、环磷酸鸟苷(cGMP)的影响,从细胞信号转导角度揭示天然药物防治白内障的细胞和分子学机制。方法:采用牛晶状体上皮细胞进行晶状体上皮细胞(LEC)原代和传代培养,以含有过氧化氢(H2 O2 )的培养液孵育LEC复制氧化损伤模型,并加入阿魏酸钠单体共同孵育。分别采用四甲基偶氮唑兰(MTT)比色测定法观察在不同时间和浓度条件下LEC活性变化,采用荧光分光光度计测定不同时间细胞内钙离子浓度([Ca2 ]i)以及放射免疫分析法测定不同时间LEC内cAMP、cGMP的含量变化。结果:H2 O2 组可引起LEC吸光度值(A)明显下降(P <0 .0 1) ,阿魏酸钠能明显增强氧化损伤的LEC活性,并呈剂量 效应关系和时间 效应关系。氧化损伤的LEC[Ca2 ]i 升高(P<0 .0 1) ;阿魏酸钠可以降低由H2 O2 引起的细胞[Ca2 ]i 的升高,并呈时间 效应关系。H2 O2 组cAMP浓度升高;cGMP浓度下降(P <0 .0 1) ;阿魏酸钠使cAMP水平下调,cGMP水平上升(P <0 .0 1) ,并呈时间 效应关系。结论:阿魏酸钠可明显抑制LEC氧化损伤及凋亡,其作用机制可能是通过钙信号系统、cAMP信号系统、cGMP信号系统及其相互作用来调节生物学效应。     

心力衰竭环核苷酸及NO的变化和相互关系的探讨

目的:观察慢性心力衰竭(CHF)患者血浆中cAMP、cGMP、NO含量的变化,阐明其在心力衰竭发生发展过程中的代偿机制。方法:用放免法测定血浆cAMP与cGMP的含量,硝酸还原酶法测NO含量。CHF组按NYHA心功能分级标准分为级、级、级进行比较分析。结果:NYHA、、级组血浆cAMP、cGMP、NO含量明显高于对照组(P<0.05),NO与cGMP存在正相关(r=0.41,P<0.05)。结论:血浆cAMP、cGMP、NO的水平和心功能不全密切相关,在不同阶段进程中,呈现动态曲线变化。可作为评价CHF患者心功能和观察疗效的一项生化指标。