氯胺酮和硝苯吡啶对培养神经元谷氨酸兴奋毒性的保护作用

以体外培养的大鼠胚胎皮层神经元为对象,以培养上清液中乳酸脱氢酶活性为指标,研究了谷氨酸兴奋毒性及药物的保护作用。结果表明,培养10d的皮层神经元置于含10或50μmol·L^-1谷氨酸和低糖(1g·L^-1)的DMEM培养液中后,随着作用时间的延长,LDH漏出逐渐增加。在谷氨酸处理前,于培养液中加入氯胺酮或硝苯吡啶,则LDH漏出量明显低于对照组。氯胺酮和硝苯吡啶并用,LDH漏出量比单独使用氯胺酮或硝苯吡啶下降更加明显。结果表明,谷氨酸对培养的神经元可产生严重损伤。氯胺酮和硝苯吡啶单用或并用均有明显的保护作用。     

硝苯地平对大鼠肺动脉高压的治疗作用及其机制探讨

[目的]探讨硝苯地平对肺动脉高压的治疗作用及其可能机制。[方法]SD雄性大鼠随机分为3组:对照组、模型组和硝苯地平治疗组。缺氧致肺动脉高压模型制作:将大鼠置于氧浓度为10％的常压缺氧箱内,每天8小时,连续4周。治疗组给予口服硝苯地平10 mg/(kg·d),模型组和对照组均给予等量生理盐水,持续4周。4周后,通过静脉插管测定血流动力学,测定右心室和肺脏肥大指数,检测血清及组织中SOD、MDA、NO水平。[结果]用药或生理盐水4周后,模型组右心室压(RVSP)和中心静脉压(CVP)均较正常组显著提高(P<0.01),而治疗组RVSP和CVP较模型组显著降低(P<0.01);经硝苯地平治疗后,均能显著抑制右心室及肺组织肥大;治疗组大鼠血液和组织中SOD和NO较模型组显著升高(P<0.01),而MDA则显著下降(P<0.05)。[结论]硝苯地平对于缺氧性肺动脉高压具有一定的治疗作用,其机制除了钙拈抗作用外,可能还存在抗氧化作用。     

高血压病患者含服硝苯吡啶后血管内皮舒张因子改变的研究

观察１０例高血压病患者含服硝苯吡啶前后血压及血管内皮舒张因子（ＮＯ）的改变，结果表明高血压病患者含服硝苯吡啶后收缩压由２２．９６±２．５９ｋＰａ下降至２０．３０±２．６２ｋＰａ，舒张压由１４．１１±１．５６ｋＰａ下降至１２．０７±１．４３ｋＰａ，差异非常显著（Ｐ均＜０．００１）；ＮＯ也由７６０．７０±２２５．９１Ｐｍｏｌ下降至６２１．５０±１９７．４３Ｐｍｏｌ，差异具显著性意义（Ｐ＜０．０５）。这提示高血压病患者含服硝苯吡啶后可降低血压，并使血管内皮衍生舒张因子（ＮＯ）减少。其次，本组结果还表明高血压病患者病程与血管内皮舒张因子呈正相关（ｒ＝０．７０２，Ｐ＜０．０５），从而提示高血压患者内皮舒张因子的调节功能减弱。     

硝苯地平联合六味地黄丸治疗原发性高血压临床观察

目的：观察硝苯地平联合六味地黄丸治疗高血压的疗效。方法：选取2009年1月～2011年1月在我院就诊的确诊为高血压的120例患者随机分为A、B、C三组各40例,A组给予六味地黄丸,B组给予硝苯地平,C组给予硝苯地平和六味地黄丸,用药18周后检测血清中免疫球蛋白IgG和补体C的变化、比较三组血压控制情况和临床症状改善。结果：三组患者的临床症状均得到改善,A组血压下降不明显,但IgG及C较治疗前降低,B组血压控制比较满意,C组血压得到理想控制。结论：硝苯地平联合六味地黄丸治疗高血压比单用硝苯地平更有效,值得临床广泛推广。     

硝苯地平缓释片联合依那普利治疗高血压病48例疗效观察

目的观察硝苯地平缓释片联合依那普利的降压作用、不良反应及对代谢的影响。方法将96例原发性高血压病患者随机分为治疗组和对照组各48例，治疗组服用硝苯地平缓释片及依那普利，对照组单纯服用依那普利，疗程4周，由固定医生测坐位血压，于治疗前后测血糖、血脂、电解质、肝功能、肾功能，并行心电图检查。结果治疗组和对照组在服药4周后显效率分别为45．8％、25．O％，总有效率分别为95．8％、68．7％，两组比较差异有统计学意义（P〈0．05或P〈0．01），而两组治疗对糖代谢、脂代谢、电解质、肝功能、肾功能及心电图并无明显影响。结论硝苯地平联合依那普利降压效果好，副作用小，值得临床推广应用。     

Synthesis and docking studies of new 1,4-dihydropyridines containing 4-(5)-Chloro-2-ethyl-5-(4)-imidazolyl substituent as novel calcium channel agonist

1,4-Dihydropyridines have been recognized as calcium channel agonist. Three new analogues of Bay K8644 in which the ortho trifluromethyl phenyl group at position 4 is replaced by the 4-(5)-Chloro-2-ethyl-5-(4)-imidazolyl substituent, were designed and synthesized as calcium channel agonist. For this propose, the structures of designed compounds were drawn by HYPERCHEM program. Conformations of the compounds were optimized through semi-empirical method followed by PM3 calculation. Then the crystalin stucture of L-type calcium channel was obtained from the Protein Data Bank (PDB) server. Docking calculations were carried out using Auto-Dock.4 program. The good interaction of our 1,4-DHP derivatives showed that they can be as possible calcium channel agonist agents. Finally compounds were synthesized according to a modified Hantzsch condensation procedure.     

Nifedipine,verapamil and cyclosporin A pharmacokinetics in children

We report two paediatric renal transplant patients in whom interaction with the calcium channel blocking agent verapamil resulted in reduced cyclosporin A (CyA) elimination. Prior therapy with another calcium channel blocking agent, nifedipine, did not affect CyA pharmacokinetics. We speculate that verapamil reduced CyA elimination in children via an effect upon the microsomal oxidase system that is independent of calcium channel activity.     

Nifedipine in hypertensive emergencies: A prospective study

Hypertensive emergencies usually present to the emergency department. Nifedipine was administered to 15 patients presenting to the emergency department with a diastolic blood pressure greater than 120 mm Hg with chest pain, shortness of breath, or focal neurological symptoms. Average blood pressure on entry was 215/134.9 mm Hg and decreased to 158/88 mm Hg over a two-hour period. No patient had any worsening of symptoms or suffered deleterious effects. All patients with pulmonary edema or chest pain noted prompt improvement in symptoms. One patient became hypotensive without clinical significance. Two patients failed to respond to nifedipine and were treated with nitroprusside. Nifedipine appears to be safe and effective in the management of hypertensive crises.     

硝苯地平联合卡托普利治疗原发性高血压临床分析

目的分析联合用药治疗原发性高血压的临床效果。方法将116例高血压患者分为两组各58例,降压饮食,合理运动的基础上,对照组口服卡托普利12.5mg,tid,观察组在口服卡托普利12.5mg,tid的同时口服硝苯地平控释片12.5mg tid,2个月1个疗程,观察血压下降情况。结果联合用药的观察组总有效率明显高于对照组,差异有统计学意义（χ2=6.56,P〈0.05）。观察组的收缩压和舒张压均明显低于对照组,差异有统计学意义（P〈0.01）;无严重不良反应发生。结论硝苯地平联合卡托普利治疗高血压,临床疗效好,无明显不良反应发生,患者耐受性好,服用方便、值得临床进行推广和应用。     

清醒家兔心绞痛模型的建立

目的：制备清醒家兔心绞痛模型,以便更好的进行抗心绞痛药物研究。方法：家兔在固定盒中适应性训练一段时间后,右前肢及双后肢电极放置区去毛,贴附带泡沫垫的 Ag/AgCl 电极,连接多导生理记录仪测定 Ⅱ 导联心电图。耳缘 iv 血管加压素 0.05 IU/kg 诱发心绞痛。并观察硝苯地平、硝酸甘油对该模型的影响。结果：清醒家兔 iv 加压素 0.05 IU/kg,可导致心电图 T 波电压升高。给予硝苯地平、硝酸甘油可减弱加压素引起的 T 波抬高。结论：该模型结果可靠,有利于抗心绞痛药物的研究。