尼莫地平含药脑脊液对体外PC12细胞损伤的保护作用

目的观察尼莫地平含药脑脊液对多种PC12细胞损伤模型的保护作用,对脑脊液药理实验条件的规范化及其应用进行探讨。方法采用噻唑蓝（MTT）法,观察不同取样时间、不同添加量、不同灭活方法处理的尼莫地平大鼠含药脑脊液对氯化钾损伤的PC12细胞存活力的影响,确定尼莫地平大鼠含药脑脊液的制备条件。并进一步考察该条件制备的尼莫地平大鼠含药脑脊液对过氧化氢、连二亚硫酸钠及谷氨酸钠等因素引起的PC12细胞损伤的保护作用。结果尼莫地平含药脑脊液对氯化钾致PC12细胞损伤的保护率随添加量的增加而提高;相同添加量多次给药（2次·d^-1×3.5d）含药脑脊液的保护率均高于单次给药的含药脑脊液;热灭活、乙醇灭活及丙酮灭活含药脑脊液对PC12细胞均有显著保护作用,其保护率与未灭活含药脑脊液无显著性差异;根据确定条件制备的尼莫地平大鼠含药脑脊液对过氧化氢、连二亚硫酸钠及谷氨酸钠等因素损伤的PC12细胞均具有显著的保护作用。结论尼莫地平含药脑脊液的制备以连续多次给药方案,无需灭活处理,体外添加终体积的10%为宜;对氯化钾等多种原因引起的PC12细胞损伤均具有明显保护作用。     

丰城鸡血藤对小鼠造血系统损伤保护作用

目的 研究丰城鸡血藤对60Co-γ射线照射小鼠造血系统损伤保护作用。方法 连续动态观察不同剂量丰城鸡血藤对小鼠经60Co-γ射线照射后1、7、14、21 d外周血白细胞、红细胞、血红蛋白和血小板的影响,同时比较21 d小鼠脾脏指数、胸腺指数变化。结果 给丰城鸡血藤治疗后小鼠外周血白细胞、红细胞、血红蛋白和血小板计数下降趋势减缓,脾脏指数和胸腺指数高于模型组(P<0.05)。结论 丰城鸡血藤可在一定程度上促进辐射损伤小鼠外周血象的恢复,保护造血系统功能。     

N—取代—2—氨基—2—噻唑啉类化合物的合成

Ｎ┐取代┐２┐氨基┐２┐噻唑啉类化合物的合成ＰＲＥＰＡＲＡＴＩＯＮＯＦＮ┐ＳＵＢＳＴＩＴＵＴＥＤ┐２┐ＡＭＩＮＯ┐２┐ＴＨＩＡＺＯＬＩＮＥＳ刚典臣＊宋俊林ａ（武汉化工学院，湖北４３００７３；ａ湖北省化学研究所，武汉４３００７４）ＧＡＮＧＤｉａｎ－Ｃｈ...     

尼莫地平对重型脑外伤患者脑血流动力学参数的影响

目的观察钙拮抗剂尼莫地平对重型颅脑损伤患者脑血流动力学参数(CVDI)的影响和指导尼莫地平的临床应用。方法选择80例重型颅脑损伤患者,按照完全随机设计分为2组。常规治疗组接受开颅手术、止血、脱水、抗炎、激素等综合治疗;尼莫地平治疗组在常规治疗的同时,加用尼莫地平治疗,连续用药达伤后30 d。采用CVA LH-450型脑血流动力学检测仪观察伤侧颈动脉血流平均速度(Vmean)、平均血流量(Qmean)、脑血管阻力和动态血管阻力。结果严重脑外伤后Vmean、Qmean明显下降,脑血管阻力与动态血管阻力明显升高。尼莫地平治疗组的上述指标均比常规治疗组有提前改善,两组有显著差异(P<0.01)。而且尼莫地平治疗组的预后明显好于常规治疗组。结论尼莫地平具有改善重型颅脑损伤患者脑血液循环及预后的作用。     

Chronic nimodipine and acute metrifonate treatment decreases age-related cortical high voltage spindles in rats

We studied the effect of nimodipine (1000 ppm mixed in food), an L-type calcium-channel antagonist, administered for 4 months, on the cortical EEG activity in young and aged rats. Nimodipine treatment decreased cortical high voltage spindles (HVSs) in aged rats, but did not prevent the diminution of spontaneous locomotor activity. The threshold dose of metrifonate, a cholinesterase inhibitor, for suppression of HVSs was lower in nimodipine compared to placebo treated aged rats (30 mg/kg versus 60 mg/kg; PO). In young rats, nimodipine did not decrease HVSs, protect from scopolamine (0.1 or 0.8 mg/kg, IP) induced EEG slowing or augment the effect of metrifonate to suppress slow waves induced by scopolamine. The present results suggest that a chronic nimodipine treatment modulates thalamocortical arousal and thereby adds to the therapeutic effects of metrifonate to restore normal cortical electrical arousal in aged rats. Received: 12 July 1996 / Final version: 9 August 1996     

Nimodipine Modulates Bcl-2 and Bax mRNA Expression after Cerebral Ischemia

In order to explore whether the member of Bcl-2 gene family, for example, Bcl-2 and Bax, are induced after cerebral ischemia, and whether expression of genes can be modulated by calcium-antagonist, the rat cerebral ischemic models were made by occluding left middle cerebral artery. The expression of Bcl-2 and Bax mRNA was measured by RT-PCR method. After middle cerebral artery occlusion (MCAO), the expression of both Bcl-2 and Bax mRNA were induced. Level of Bcl-2 mRNA increased steadily and level of Bax mRNA increased gradually at first, reached a peak after 24 h, then decreased slowly. After administration of nimodipine, Bcl-2 mRNA was up-regulated in the hippocampus 6 and 24h after ischemia, while Bax mRNA was down-regulated 6 and 24 h after ischemia. Focal cerebral ischemia can induce proto-oncogenes to express, which was associated with apoptosis. Calcium-antagonist can up-regulate Bcl-2 mRNA and down-regulate Bax mRNA.The increased ratio of Bcl-2 and Bax mRNA may contribute to the antiapoptic effect of nimodipine.The study indicates that pharmacological modulation of Bcl-2 family member expression could become a new stratehgy to manage neuronal damage.     

单唾液酸神经节苷脂对大鼠脑血管痉挛后局部脑血流量与微血管的影响

目的　观察单唾液酸神经节苷脂 (GM1)对脑血管痉挛 (CVS)后局部脑血流量 (rCBF)与微血管的影响 ,以探讨其防治CVS的可能性。方法　将 2 5只大鼠随机分为对照组、CVS组、尼莫地平组 (Nim组 )、GM1治疗组 (GM1 T组 )、GM1预防组 (GM1 P组 )。运用蛛网膜下腔二次注血制备CVS模型。每组分别于二次注血后 0h、0 5h、1h、3h及 6h测量rCBF ;6 5h后断头取脑 ,抗Ⅷ因子相关抗原免疫组化染色标记微血管 ,图像分析观察颞叶皮质微血管的数密度、面密度。结果　 (1)rCBF :二次注血后CVS组、Nim组、GM1 T组的rCBF明显下降 (均P <0 0 1) ,6h时Nim组、GM1 T组的rCBF回升至注血前水平 ,CVS组的rCBF无明显回升 ;GM1 P组在二次注血后rCBF无明显下降。 (2 )图像分析 :CVS组的微血管数目、面积及平均面积均减少 (均P <0 0 1) ;Nim组的微血管面积较对照组、CVS组明显增加 (均P <0 0 1) ;GM1 T组的微血管数目、面积及平均面积较对照组、CVS组显著增加 (均P <0 0 1) ;GM1 P组的微血管数目、面积及平均面积增多最明显 ,与CVS组比较差异有极显著性 (均P <0 0 1)。结论　蛛网膜下腔二次注血可降低rCBF、减少皮质微血管数目和面积 ,诱发CVS,尼莫地平可缓解CVS程度 ,但GM1的治疗作用比尼莫地平更强 ,并能预防CVS的发生     

东亚钳蝎蝎毒二级提取物XIII－2的钠通道阻滞作用

培养小鼠心肌细胞。用微电极胞内引导快反应心肌细胞动作电位。东亚钳蝎蝎毒二级提取物ＸＩＩＩ－２３μＧ·Ｍｌ－１使心肌细胞动作电位的除极有关参数全部减小，对动作电位时程与发放频率无影响。此效应于洗脱后立即消失。实验性钠通道失活同样使除极有关参数减小。应用钙通道阻滞剂后除极有关参数无改变。结果表明：ＸＩＩＩ－２有单纯钠通道阻滞作用。     

Effects of extracellular calcium and of the calcium entry blockers flunarizine and nimodipine on contractile responses in human temporal arteries

Contraction induced by 124 mM potassium followed the depolarization of smooth-muscle cells and activation of potential-operated calcium channels in human temporal arteries. The contraction elicited consisted of two phases, one rapid and one slowly developing stable phase; both were affected by the two calcium entry blockers flunarizine and nimodipine but at significantly different concentrations. In calcium-free medium 124 mM potassium resulted in a weak contraction. Addition of calcium caused a concentration-dependent contraction that was attenuated by the calcium entry blockers at concentrations comparable to those inhibiting the second phase. The results suggested that in human temporal arteries flunarizine and nimodipine act as calcium entry blockers; there was good correlation with the therapeutic plasma concentration for nimodipine but not for flunarizine.     

尼莫地平片的药动学及生物等效性

目的 :研究尼莫地平片的药动学和相对生物利用度 ,验证该制剂与进口尼莫地平片的生物等效性。方法 :采用HPLC法测定 2 4名健康男性志愿者自身交叉单剂量口服国产尼莫地平片和进口尼莫地平片 12 0mg的经时血药浓度 ,计算主要药动学参数以及受试制剂的生物利用度。结果 :国产尼莫地平片和进口尼莫地平片的血药浓度 时间曲线符合一室模型 ,其主要药动学参数 :Cmax分别为 (83.9± 15 .4) μg·L-1与 (83.5± 12 .8) μg·L-1,Tmax分别为 (0 .5 7± 0 .0 6 )h与 (0 .6 7± 0 .0 8)h ,T1/2ke分别为 (1.80± 0 .16 )h与 (1.6 9± 0 .17)h ,AUC0 -t分别为 (16 0 .9± 15 .8) μg·h·L-1与 (15 6 .2± 18.7) μg·h·L-1。国产尼莫地平片对进口尼莫地平片的相对生物利用度为 (10 8.0± 7.2 ) %。结论 :国产尼莫地平片与进口尼莫地平片生物等效