间硝地平对左室肥厚大鼠左室舒张功能及心脑线粒体和血管组织钙含量的影响

用肾性高血压左室肥厚(LVH)大鼠模型,观察了间硝地平(m-Nif)和硝苯地平(Nif)长期给药(ig20mg·kg^-1·d^-1持续9周)对左室舒张功能、左心室肌和大脑线粒体及血管钙含量的影响。与假手术组相比,LVH组左室顺应性明显下降,僵硬度增高,左心室肌和大脑线粒体及尾动脉和主动脉钙含量增加。与LVH组相比,m-Nif和Nif各组左室顺应性改善,僵硬度降低(P<0.01),左心室肌线粒体及尾动脉和主动脉钙含量较LVH组显著降低(P<0.01)。两药在作用强度上无显著差异。     

硝苯啶长期应用对肝硬变肝血流及肝功的影响

目的研究钙通道阻滞剂硝苯啶（ＮＦＰ）长期口服对３２例肝硬变门脉高压患者肝血流及肝功的影响．方法采用无创伤性核多功能仪首次通过法观察肝血流，同时记录服药前后体循环及肝功等变化．结果ＮＦＰ口服４周以上，总体患者及Ｃｈｉｌｄ＿Ｐｕｇｈ分级的各级患者均显示可明显减少门脉血流（ｋｖ），使肝动脉血流（ｋａ）增加，而不影响肝脏的总血流（ｋａ＋ｋｖ）；对平均动脉压（ＭＡＰ）及心率（ＨＲ）等体循环的影响甚小，并可改善血清白蛋白、胆红素及ＡＬＴ水平．结论ＮＦＰ可长期用于临床降低肝硬变门脉高压，预防食管曲张静脉破裂出血     

硝苯地平对冠心病左室收缩功能和舒张功能的影响

目的 :用脉冲多普勒超声心动图评价硝苯地平对冠心病左室收缩功能和舒张功能的影响。方法 :研究组包括 39例冠心病心绞痛患者 ,2 8例陈旧性心肌梗塞患者 ;同时选择 35例正常人作为正常对照组。正常对照组及冠心病组于治疗前及治疗后 3d、一个月分别进行心功能测定。结果 :冠心病患者的左室收缩功能基本正常 ,左室舒张功能减退 (P <0 0 1) ;应用硝苯地平治疗 3d及一个月后 ,左室收缩功能无明显改变 ,左室舒张功能明显改善。结论 :硝苯地平可以明显改善冠心病患者的左室舒张功能。A峰 /E峰 >1 2 8,IA/IE >0 9及IRP >90ms可以做为判定左室舒张功能损害的标准。这些多普勒参数可以为早期无创性诊断冠心病提供依据。     

Separation of calcium currents in retinal ganglion cells from postnatal rat

A culture system of the postnatal rat retina was established to investigate Ca²⁺ currents and synaptic transmission in identified neurons. Methods are described that allowed us to select retinal ganglion neurons (RGNs) in short term cultures (up to 48 h in vitro) and in long-term cultures (3 to 21 days in vitro). The specific aim of the present study was to identify channel specific components in whole-cell Ca²⁺ currents of RGNs and to clarify the potential use of the lanthanide Gd³⁺ as a selective Ca²⁺ channel blocker. About one third of freshly dissociated RGNs generated both low voltage activated Ca²⁺ currents (I_Ca(LVA)) and high voltage activated Ca²⁺ currents (I_Ca(HVA)). The remaining 2/3 of RGNs in short term culture and most RGNs in long-term culture displayed only I_Ca(HVA). The latter comprised at least three different components that were functionally rather similar, but could be separated pharmacologically. A significant portion (about 40%) of I_Ca(HVA) was irreversible blocked by the N channel antagonist ω-CgTx (5 μM). The L channel antagonist nifedipine (10 μM) eliminated about 25% of I_Ca(HVA). Thus, about 1/3 of the HVA Ca²⁺ or Ba²⁺ current remained unaffected by either ω-CgTx or nifedipine. ω-AgaTx (200 nM) completely failed to block HVA Ca²⁺ or Ba²⁺ currents in RGNs. Gd³⁺ exerted contrasting actions on LVA and HVA Ca²⁺ currents. While I_Ca(LVA) consistently increased in the presence of Gd³⁺ (0.32–3.2 μM), I_Ca(HVA) always decreased, especially when using higher concentrations of Gd³⁺ (10–32 μM). The blocking action of Gd³⁺ was not restricted to the ω-CgTx-sensitive HVA current component, but also concerned ω-CgTx- and nifedipine-resistant components. The decay of Ca²⁺ currents was accelerated in the presence of Gd³⁺. Even in RGNs lacking I_Ca(LVA), application of 3.2 μM Gd³⁺ significantly reduced the time constant of decay from an average of 64 ms to 36 ms (voltage steps from −90 to 0 mV; 10 mM [Ca²⁺]₀; 26°C). This is in contrast to what had to be expected if an N-type HVA current component was selectively suppressed by Gd³⁺. Gd³⁺ diminished glutamatergic spontaneous synaptic activity in retinal cultures tested during the 3rd week in vitro. Both frequency and amplitude were reduced. Occasionally, the application was followed by a rebound increase of EPSC frequency. A stimulatory effect during application of Gd³⁺ has never been observed. These experiments indicate that RGNs express at least 4 different types of Ca²⁺ currents, that resemble in some aspects T, N and L channel currents. A significant component of the HVA Ca²⁺ current was resistant to the available HVA channel blockers suggesting the presence of a pharmacologically distinct type of HVA Ca²⁺ channel type in RGNs. Our experiments also show that Gd³⁺ is not suitable for isolation of HVA subcomponents in RGNs, but it can be used to distinguish between LVA and HVA Ca²⁺ currents, as these currents reacted to Gd³⁺ in an opposite way. The purely depressive effect of this lanthanide on spontaneous synaptic activity is consistent with the assumption that in retinal neurons LVA Ca²⁺ channels are not involved in the regulation of glutamate release.     

硝苯吡啶乳膏的研制及其经皮给药治疗高血压的临床疗效

笔者研制的o/w 型硝苯吡啶乳膏,以二甲亚砜和1,2-丙二醇为透皮促进剂,经皮给药治疗高血压病人22例,显效14例,有效7例,总有效率95.45％。用药后4.19±1.62min血压开始下降,22.14±8.74min血压下降达最大值,降压效应持续5.71±2.17h。降压起效时间比氮酮硝苯吡啶乳剂快58.26倍,比口服给药快4.77倍,与口含相当。心率在用药后明显下降(p<0.05),与许多报道不一致,可能与用药方式和给药途径有关。     

PKC和ROCK对硝苯地平舒张血管作用的影响

目的:探讨蛋白激酶C(PKC)及Rho相关激酶(ROCK)对硝苯地平舒张大鼠离体胸主动脉血管环作用的影响。方法:采用离体血管环灌流装置观察硝苯地平对基础状态血管环及去甲肾上腺素(NE,10~(-6)mol/L)或KCl(60mmol/L)预收缩血管环的张力变化,并利用PKC抑制剂和ROCK抑制剂等工具药观察对硝苯地平舒血管作用的影响并探讨可能机制。结果:系列浓度硝苯地平对基础状态血管环张力无明显影响,对NE和KCl预收缩的血管环具有浓度依赖性舒张作用(P 0. 05),去内皮组舒张作用与内皮完整组比较无明显差异。预孵PKC抑制剂星孢菌素(STA,10~(-8)mol/L)及激动剂佛波酯(PMA,10~(-7)mol/L)后,STA能增强硝苯地平对血管的舒张作用,而PMA能减弱硝苯地平对血管的舒张作用(P 0. 05);预孵ROCK抑制剂法舒地尔(fasudil,10~(-6)mol/L)及激动剂血管紧张素Ⅱ(Ang-Ⅱ,10-9mol/L)后,fasudil能增强硝苯地平对血管的舒张作用,而Ang-Ⅱ能减弱硝苯地平对血管的舒张作用(P 0. 05);钾通道阻滞剂BaCl_2(10~(-4)mol/L)、四乙胺(10~(-3)mol/L)、格列本脲(10~(-5)mol/L)和4-氨基吡啶(10~(-3)mol/L)对硝苯地平的舒张血管作用无明显影响。在无钙且含高浓度KCl的溶液中,硝苯地平可浓度依赖性地抑制累积浓度的CaCl_2对大鼠离体主动脉环的收缩作用(P 0. 05)。在无钙液中,硝苯地平对NE所引起的收缩无明显影响。结论:硝苯地平能够呈浓度依赖性地舒张大鼠主动脉,其舒张血管作用为非内皮依赖性,且与抑制细胞外钙内流密切相关,其舒张血管作用部分与抑制PKC和ROCK作用相关。     

拜新同与北京降压0号或海捷亚合用治疗老年性单纯性收缩期高血压疗效观察

目的：观察和分析拜新同分别联合北京降压0号或海捷亚治疗老年性单纯性收缩期高血压（ISH）的疗效及对代谢的影响。方法：选择83例老年ISH患者随机分为3组，拜新同组（A组，n=28，拜新同30mg，1次／d），拜新同与北京降压0号合用组（B组，n=28，拜新同30mg，1次／d，北京降压0号1片，1次／d），拜新同与海捷亚合用组（C组，n=27，拜新同30mg，1次／d，海捷亚50mg，1次／d）。3组治疗疗程均为12周，观察3组治疗前后的血压及肝肾功能、血糖、血脂、电解质等指标的变化。结果：B、C组降压总有效率相当，其对随测血压、24h动态血压的控制疗效接近；B、C组血压控制效果明显优于A组；3组治疗前后心率及生化指标无明显改变。结论：拜新同与北京降压0号或海捷亚合用降低老年ISH均有较显著且相似的疗效．与单用拜新同比较效果更好。     

拜新同与科素亚或海捷亚合用的降压疗效观察

目的研究和评价拜新同与科素亚或海捷亚合用降压疗效及对代谢的影响。方法选择45例中、重度原发性高血压患者,随机分成3组,每组各15例。拜新同组:单用拜新同30mg,每日1次;拜新同与科素亚合用组:拜新同30mg,每日1次,加科素亚50mg,每日1次;拜新同与海捷亚合用组:拜新同30mg,每日1次,加海捷亚50mg,每日1次。3组疗程均为12周。观察3组治疗前后的随测血压(CBP)和24h动态血压(ABPM)及生化指标。结果拜新同加海捷亚组降压总有效率及CBP、ABPM的变化均明显优于拜新同单用组和拜新同与科素亚合用组。治疗前后心率和生化指标则无明显改变。结论拜新同与海捷亚联合应用降低中、重度高血压效果较单用拜新同组以及拜新同和科素亚合用组更有效,且对代谢无影响。     

硝苯地平治疗单纯收缩期高血压有效性和安全性的系统评价

目的评价单用硝苯地平治疗单纯收缩期高血压(ISH)的有效性和安全性。方法计算机检索Cochrane Library(2013年第5期),PubMed、EMbase、CBM、EMCC、CNKI、VIP和WanFang Data等数据库,检索时限从1996年1月至2013年6月。文献的质量评价按照Cochrane系统评价手册进行,使用RevMan 5.0软件进行系统评价。结果最终纳入6篇随机对照试验进行分析,合计695例患者。Meta分析结果显示:1降压有效率:硝苯地平缓释片较复方降压片高,差异有统计学意义[RD=0.26,95%CI(0.11,0.40),P0.05],其余各组差异无统计学意义。2不良反应/事件发生率:硝苯地平片与尼莫地平片[RD=0.02,95%CI(-0.16,-0.19),P=0.83],硝苯地平控释片与苯磺酸氨氯地平片[RD=0.05,95%CI(-0.01,0.10),P=0.12],硝苯地平缓释片与复方降压片[RD=-0.10,95%CI(-0.24,0.04),P=0.18]比较,差异无统计学意义。结论本系统评价显示治疗ISH疗效:1硝苯地平缓释片强于复方降压片;2硝苯地平控释片与苯磺酸氨氯地平片相似,但弱于吲达帕胺片;3硝苯地平片与尼莫地平片相似。单用硝苯地平治疗ISH的不良反应可以接受。     

硝苯地平缓释片与硝苯地平控释片的降压疗效观察

目的:探讨硝苯地平缓释片(SR)与硝苯地平控释片(GITS)对高血压的降压效果及对生化指标影响。方法:利用动态血压监测(ABPM)对32例Ⅰ、Ⅱ级高血压病人服用硝苯地平SR和GITS时进行血压检测。结果:硝苯地平SR、GITS均有明显降压效果(P均<0.01),硝苯地平GITS较硝苯地平SR表现出较大的降压谷/峰比及较少的血压变异性(P<0.05)。两者对大部分血生化指标无明显影响。结论:硝苯地平GITS是更高效、平稳、安全的降压药。