Ligustrazine inhibits high voltage-gated Ca~(2+) and TTX-resistant Na~+ channels of primary sensory neuron and thermal nociception in the rat:a study on peripheral mechanism

Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinoci-ceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency ( PWL) to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion (DRG) neurons. Results Intraplantar injection of ligustrazine (0.5 mg in 25μl) significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion (DRG) neuron in dose-dependent manner with IC50 of 1.89 mmol/L, but also decreased tetrodotoxin (TTX) -resistant sodium current in relatively selective and dose-dependent manner with IC50 of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron in the rat.     

川芎嗪的药动-药效学研究近况

川芎嗪是一种活性生物碱，其在体内代谢迅速，排泄较快，临床应用广泛，综述了近几年的药效学及药动学研究成果，并提出存在问题和未来研究的前景。     

Effect of Ligustrazine on Bone Marrow Microenvironment and Signal Transducti on Path in Irradiation Injured Mice

Ｗｅｈａｖｅｒｅｐｏｒｔｅｄ ｐｒｅｖｉｏｕｓｌｙｔｈａｔｌｉｇｕｓｔｒａｚｉｎｅｃｏｕｌｄｐｒｏｍｏｔｅｈｅｍａｔｏｐｏｉｅｓｉｓｔｈｒｏｕｇｈｉｍｐｒｏｖｉｎｇｂｏｎｅｍａｒｒｏｗｍｉｃｒｏｅｎｖｉｒｏｎｍｅｎｔａｎｄｅｎｈａｎｃｉｎｇａｄｈｅｓｉｖｅ     

The Effect of Ligustrazine on Peritoneal Transport in Peritoneal dialysis

In order to investigate the effect of ligustrazine (Lig)i.p.on peritoneal permeability in peritoneal dialysis and its side effects,creatinine was given intravenously and continuously to maintain the high plasma creatinine level.All the rabbits were divided into three groups:normal control group (goup A),group B treated with 0.12% Lig and group C treated with 0.24% Lig.The peritoneal dialysis of all rabbits lasted 2h.The plasma and dialysate levels of glucose,protein and creatining were observed immediate,30min,60min,90min,120min after dialysis.Creastinine dialysate/plasma ratio (D/P),protein D/P ratio,grucose D/Do at different time points after dialysis and creatinine mass transfer area coefficient (MTAC) at 120min were calculated.The structures of peritoneum were observed under optical microscope and electron microscope after continuously intraperitoneal injection of Lig for 14 days.The results showed that the 90-min and 12-min creatinine D/P ratios in the group C were higher than in the group A.The 120-min creatinine MATC in the group C was higher than in the group A.The rabbits treated with Lig did not show significant structure changes of peritoneum and signs of peritoneal irritation.It was suggested that Lig could increase mass transfer ability of peritoneum without significant side effects.     

川芎嗪对环孢素引起的大鼠胰岛β细胞毒性防护作用的实验研究

给大鼠应用环孢素(CsA)50mg/kg·d灌胃,共10天,引起高血糖症及血浆和胰腺组织中胰岛素水平下降。同时联合应用川芎嗪(LIG)50mg/kg·d共10天,能有效地防止和(或)减轻CsA引起的上述变化。LIG还有效地减轻了CsA引起的尿血栓素B_2和尿血栓素B_2/6-酮-前列腺素F_(1α)值的升高。结果提示LIG对CsA引起的胰岛β细胞毒性的防护作用可能与调节前列胰素代谢有关。     

川芎嗪对肺血管的舒张作用

本实验比较了川芎嗪对不同段的肺血管的舒张作用,结果表明川芎嗪对肺实质内动脉的舒张作用比肺实质外动脉强,内皮细胞能促进川芎嗪对肺动脉的舒张作用。     

川芎嗪、山莨菪碱、蝮蛇抗栓酶及卡托普利对糖尿病大鼠肾脏的保护作用

目的　探讨川芎嗪、山莨菪碱、蝮蛇抗栓酶及卡托普利对实验大鼠糖尿病肾病 (DN)的预防作用。方法　SD大鼠 6 0只 ,分为正常对照组、糖尿病组及各糖尿病治疗组。以四氧嘧啶腹腔内注射制成糖尿病模型。各治疗组分别给予上述药物治疗 ,每周 5次 ,共 14周。取肾脏行光镜和电镜检查 ,并进行图像分析 ,同时测定蛋白糖基化产物 (GP)。结果　与糖尿病组比较 ,各治疗组肾组织中水平明显降低 (P <0 .0 1) ;除蝮蛇抗栓酶组外 ,其他治疗组大鼠肾小球截面积亦明显缩小 (P <0 .0 5 ) ;糖尿病组大鼠肾小球基底膜显著不均匀增厚 ,而各治疗组病变较轻 ,尤以卡托普利组疗效最为明显。结论　改善微循环、血液流变学及血流动力学治疗可减慢实验大鼠DN的进展。     

川芎嗪与前列腺素E1联合治疗慢性肺源性心脏病急性发作期疗效观察

目的 观察联用川芎嗪（ＬＴ）和前列素（ＰＧＥ４）治疗慢性肺源性心脏病（肺心病）急性发作期患者的临床疗效。方法 １０５例肺心病急性发作期患者随机分为治疗组（５４例）和对照组（５１例）,治疗组采用ＬＴ联合ＰＧＥ１治疗;对照组采用单纯ＰＧＥ１治疗。２组患者于治疗后１０ｄ测定血液流变学指标并进行疗效判定。结果 治疗组显效率（５９．２６％）明显高于对照组（３９．２２％）,２组比较具有显著差异（Ｐ〈０．０５）     

川芎嗪及其衍生物对羟自由基的清除作用

目的:探讨川芎嗪及其衍生物对羟自由基的清除作用。方法:应用Fenton反应检测并计算50％羟自由基被清除时的药物浓度(EC_(50))。结果:结果显示对羟自由基均有明显清除作用,且呈剂量依赖关系。川芎嗪及其衍生物与苯甲酸和甘露醇的清除作用差异有极显著性(P<0.01),而相互间作用无明显差异(P>0.05)。结论:川芎嗪及其衍生物对羟自由基有明显的清除作用。     

聚氯乙烯软袋对腹膜透析液中川芎嗪的吸附

 目的：考察聚氯乙烯（PVC）软袋装川芎嗪在腹膜透析液中的稳定性。方法：含川芎嗪0．04mg·ml^－1和0．20mg·ml^－1的腹膜透析液分别置于4℃，25℃和37℃，定时取样以HPLC测定含量，药物浓度降低≤5％为稳定性指标。结果：由于PVC软袋的吸附作用，各浓度在25℃ 6h后均有显著性降低，12h后降至95％以下；37℃ 4h即均有显著性降低，8h后降至95％以下。0．20mg·ml^－1（4℃）在24h后浓度明显下降，但10d后浓度下降未超过5％，0．04mg·ml^－1（4℃）在观察期间浓度略有升高。结论：PVC软袋可吸附川芎嗪，随温度的升高，吸附作用亦增强。川芎嗪溶于腹膜透析液后室温贮放不宜超过6h，温度升至37℃后尽快使用。