苏合香对大鼠急性局灶性脑缺血损伤的作用初探

Effects of Storax on focal cerebral ischemia in rats

关键词:  苏合香  药理预适应  局灶性脑缺血  安全评价  药效评价

Key words:  Storax  pharmacologic preconditioning  focal cerebral ischemia  safety evaluation  efficacy evaluation

摘要:

[目的] 研究苏合香预处理对健康大鼠生理状态下的安全性及急性局灶性脑缺血病理损伤状态下的反应性, 初步探索苏合香药理预适应对急性脑缺血损伤的影响, 为阐明苏合香“开窍”作用提供部分实验依据。[方法] 将健康雄性SD大鼠随机分为假手术组(Sham)、对照组(Vehicle)及苏合香各剂量组[Storax 0.1、0.2、0.4、0.8、1.6 g/(kg·d)].监测预给药期间各组大鼠体质量及肝肾功能以确保用药安全性。预给药5 d后, 线栓法建立大鼠大脑中动脉阻塞(MCAO)模型, 激光多普勒血流检测仪(LDF)监测脑血流以评价、筛选模型, 于缺血24 h时评价药效:改进的ZeaLonga神经功能评分评价神经功能缺损, 2,3,5-氯化三苯基四氮唑(TTC)染色评价脑梗死体积、半球水肿率, 并计算总死亡率, 同时检测凝血四项以观察大鼠脑缺血急性期凝血功能。[结果] Storax 1.6 g/(kg·d)组连续灌胃给药数日后, 大鼠体质量较同时同点其他各组体质量明显降低(P<0.05),血浆谷丙转氨酶(ALT)、尿素(CREA)水平显着升高(P<0.05),故于后续实验中取消该组以确保用药安全;与对照组比较, Storax 0.1、0.2、0.4、0.8 g/(kg·d)各组能显着降低大鼠脑缺血后半球水肿率及神经功能评分(P<0.05),Storax 0.2、0.4、0.8 g/(kg·d)各组能显着降低脑梗死体积比(P<0.05),并有降低死亡率的趋势;Storax 0.2、0.4、0.8 g/(kg·d)各组能显着延长血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)并降低纤维蛋白原(FIB)含量(P<0.05).[结论] 苏合香药理预适应可使大鼠急性局灶性脑缺血后病理损伤程度减轻, 显示其潜在的抗脑缺血作用前景, 其抗脑缺血损伤作用可能与苏合香通过改善缺血后血液高凝状态而改善脑血流有关, 或为苏合香“开窍”机制之一;Storax 0.8 g/(kg·d)组同时具有药理作用及部分毒理作用, Storax 0.1、0.2、0.4 g/(kg·d)组所用剂量可视为相对安全、有效。

Abstract:

[Objective] To investigate effects of Storax on acute focal cerebral ischemia in rats. [Methods] Healthy male SD rats were administered intragastrically with Storax at the dose of 0.1, 0.2, 0.4, 0.8 and 1.6 g/kg in each day, for 5 days, and then induced with occlusion of middle cerebral artery (MCAO) with suture embolus. Body weight and hepatic-renal function of healthy rats during pretreatment were measured before stroke, and ischemic infarct volumes and hemispheric swelling rates were quantified on TTC-stained brain slices at 24 h, after stroke, also, neurological scores, death rates and the content of Fib, PT, APTT, TT were evaluated 24 hours after stroke. [Results] Rats treated with storax at the dose of 1.6 g/kg in each day presented signs of toxicity, weight growth were decreased and ALT, CREA were increased compared with other groups (P<0.05), and 0.1, 0.2, 0.4, 0.8 g/kg in each day were chosen as the relatively safety doses to proceed the subsequent experiment. 24 hours after stroke, the infarct volumes, hemispheric swelling rates and neurological deficits of rats in the vehicle group were significant compared with the sham group (P<0.05), and Storax significantly attenuates the brain damage of cerebral ischemia (P<0.05). Compared with the sham group, the concentration of Fib significantly increased (P<0.05) and PT, APTT, and TT significantly shortened in the model group (P<0.05);however, compared with the vehicle group, Storax significantly decreased Fib content (P<0.05) and prolonged PT, APTT (P<0.05). [Conclusion] Storax can attenuate the brain damage and regulate the coagulation function in acute focal cerebral ischemia in rats.