磷酸川芎嗪与盐酸川芎嗪对大鼠局灶性脑缺血模型的作用比较
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摘要：目的比较磷酸川芎嗪和盐酸川芎嗪治疗阻断大鼠大脑中动脉所致大脑局灶性脑缺血模型的疗效。方法随机将大鼠40只分为伪模型组、模型对照组、磷酸川芎嗪组、盐酸川芎嗪组。用线栓法阻断大鼠大脑中动脉制备局灶性脑缺血模型，手术后分别按10 mL/kg静脉给药，12 h后对其神经症状评分，24 h后处死动物取脑，TTC染色，计算梗死面积，并行病理组织学检测。结果磷酸川芎嗪和盐酸川芎嗪均可明显降低模型大鼠大脑梗死面积和梗死率，明显减轻模型大鼠的神经症状，抑制神经元变性坏死和神经细胞水肿等病理组织学改变；与对照组的差异有统计学意义，但2种药物比较无统计学差异。结论用磷酸川芎嗪和盐酸川芎嗪治疗脑梗死基本等效。
关键词：磷酸川芎嗪；盐酸川芎嗪；局灶性脑缺血
中图分类号：R743.31文献标识码：A文章编号：1672-979X(2008)09-0037-03
Comparative Study on Effect of Ligustrazine Phosphate and Ligustrazine Hydrochloride on Focal Cerebral Ischemic Rats
CAO Yan-hua，LIU Shan-shan
(Provincial Hospital Affiliated to Shandong University, Jinan 250022, China)
Abstract：Objective To compare the curative effect of ligustrazine phosphate and ligustrazine hydrochloride on focal cerebral ischemia induced by middle cerebral artery occlusion in rats. Methods Forty Sprague-dawley rats were randomly divided into four groups: normal control group, model control group, ligustrazine phosphate group and ligustrazine hydrochloride group. The focal cerebral ischemic model was induced by middle cerebral artery occlusion with intraluminal thread method in rats. After surgery, the rats were treated with different solution 10 mL/kg by intravenous administration. Nervous symptom score was measured at 12 hours after operation. The rats were sacrificed and the brains were removed at 24 hours after operation, then, the cerebral infarct area was calculated by TTC staining and the histopathological examination ofbrains was detected. Results Compared with the control groups, ligustrazine phosphate and ligustrazine hydrochloride could significantly reduce infarct area and infarct rate, relieve nervous symptom, inhibit neuronal degeneration and neurocyte edema, and the difference was statistically significant. However, there was no statistical difference between ligustrazine phosphate group and ligustrazine hydrochloride group. Conclusion The curative effect of ligustrazine phosphate on focal cerebral ischemia is equivalent to that of ligustrazine hydrochloride.
Key words：ligustrazine phosphate; ligustrazine hydrochloride; focal cerebral ischemia
磷酸川芎嗪和盐酸川芎嗪均有抗血小板聚集和解聚，扩张小动脉，改善微循环、增加脑血流和活血化淤的作用，临床上常用于缺血性脑血管疾病，如脑供血不足、脑血栓形成、脑栓塞等[1,2]。二者的注射剂在我国有多个药品批准文号，由于疗效确切、副作用小，临床上广泛使用。我们通过大鼠局灶性脑缺血模型比较了磷酸川芎嗪和盐酸川芎嗪的药理作用[3]。
1试验材料
1.1供试品
注射用磷酸川芎嗪(规格：50 mg，苏州二叶制药公司，070505)；盐酸川芎嗪注射液(规格：2 mL：40 mg，天津金耀氨基酸公司，0608032)。
1.2主要仪器及试剂
AY220型电子分析天平(岛津)；YB502型电子天平(上海海康电子仪器厂)；DMLS2显微镜(德国Leica公司)。
红四氮唑(TTC，中国医药上海化学试剂公司)；磷酸氢二钾(天津市广成化学试剂公司)；水合氯醛(青岛宇龙海藻公司)。
1.3实验动物
SD大鼠，40只，250～300 g，雄性(山东鲁抗医药公司提供，许可证号：SCXK[鲁]20050017)。
2试验方法
2.1分组
按体重随机将健康大鼠40只分为4组，即伪模型组、模型对照组、磷酸川芎嗪组、盐酸川芎嗪组，每组10只。磷酸川芎嗪组、盐酸川芎嗪组的用药剂量分别为9 mg/kg 和7.2 mg/kg，按川芎嗪计二者给药剂量相当，均按10 mL/kg静脉注射给药。
2.2试验过程
大鼠腹腔注射水合氯醛(350 mg/kg)麻醉，仰卧固定，沿颈正中作约2 cm长的切口，分离右侧颈总动脉并穿缝线2根备用，再分离颈外动脉结扎。在颈外动脉下方小心分离颈内动脉。结扎分离的颈总动脉近心端，用微动脉夹暂时阻断远心端血流，于颈总动脉上剪一小口，将鱼线插入小口，取下动脉夹，将鱼线缓慢推至前脑动脉(约20 mm)再回拉约2 mm即至大脑中脑动脉口，长约18 mm(自颈内外动脉分叉处算起)，用缝线结扎固定鱼线。缝合肌肉和皮肤，手术完毕后立即给予相应的药物溶液10 mL/kg ......
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