再造丸塞隆骨替代豹骨后抗脑缺血效应机制的研究

Effect of Zaizao Wan( Sailong Bone Replacement of Leopard Bone) Against Cerebral Ischemia

目的:观察塞隆骨替代豹骨后再造丸抗脑缺血的效应机制,为替代合理性提供药理学实验数据支持。方法:采用小鼠断头急性脑缺血实验和小鼠双侧颈总动脉结扎法造模,观察塞隆骨替代豹骨后再造丸(以下简称再造丸替代后)对小鼠急性脑缺血的影响。采用大鼠线栓法大脑中动脉阻塞(MCAO)脑缺血模型,观察再造丸替代后对大脑梗塞面积、神经功能评分以及对丙二醛(MAD),超氧化物歧化酶(SOD)和一氧化氮(NO)的影响。采用"胶原蛋白-Adr"诱发小鼠体内血栓形成模型观察偏瘫形成率和死亡率;采用急性血瘀模型大鼠管观察血液流变学及血小板聚集率,评价再造丸替代后的活血化瘀作用。结果:再造丸替代后可增加小鼠断头后急性脑缺血的呼吸次数和呼吸持续时间,与再造丸组比较无显著性差异;可显著延长双侧颈总动脉结扎法小鼠急性脑缺血的存活时间,与再造丸组比较无显著性差异。可显著减小MCAO大鼠梗塞面积;降低缺血后4,24 h模型大鼠神经功能行为学评分;各给药组均可显著降低模型大鼠血清MDA含量;低剂量组可提高MCAO模型大鼠血清SOD活力;各剂量组均可显著升高大鼠血清NO水平,且优于再造丸组。可减少尾静脉注射"胶原蛋白-Adr"形成体内血栓所致小鼠5 min内的死亡率,提高15 min内的偏瘫恢复率。可降低血瘀模型大鼠全血血流变切变率降低ADP诱导的血小板聚集率。结论:再造丸替代后对脑缺血有保护作用,保护机制可能与其调节抗氧化能力及改善血流变学有关。

Objective： To observe the mechanism of Zaizao Wan Sailong bone replacement of leopard bone against cerebral ischemia,and provide experimental pharmacology data for replacement rationality. Method：The decapitation ischemia experiment and bilateral carotid artery ligation were used to establish mice models and observe the effect of Sailong bone Zaizao Wan（ hereinafter referred to as Sailong bone Zaizao Wan） on acute cerebral ischemia in mice. Middle cerebral artery occlusion（ MCAO） cerebral ischemic models were induced by using suture-occluded method. The effect of Sailong bone Zaizao Wan on infract area,neurological scores,malondialdehyde（ MDA）,superoxide dismutase（ SOD） and nitric oxide（ NO） levels in serum were observed.‘Collagen-Adr＇was used to induce thrombosis mice models and observe hemiplegia formation rate and mortality.Acute blood stasis rat models were used to observe hemorheology and platelet aggregation rate,and evaluate the effect of Sailong bone Zaizao Wan on activating blood circulation and dissipating blood stasis. Result： Sailong bone Zaizao Wan can increase breathing time and frequency of mice with acute cerebral ischemia after decollation,with no significant difference with Zaizao Wan group; and can significantly prolong the survival time of bilateral carotid artery ligation in mice with acute cerebral ischemia,with no significant difference with Zaizao Wan group. Sailong bone Zaizao Wan could significantly decrease the infarct size in MCAO rats,and 4,24 hours after ischemia,neurological function scores were decreased. Various treatment groups could significantly reduce serum MDA level in model rats; low dose group could improve serum SOD activity in MCAO model rats; various dose groups could significantly increase serum NO level in rats and the effect was better than Zaizao Wan group. Sailong bone Zaizao Wan could reduce the mortality within 5 min induced by tail intravenous injection of ＂collagen-Adr ＂thrombus formation,and increase the hemiplegia recovery rate within 15 min. It could decrease the whole blood flow shear rate and reduce ADP-induced platelet aggregation rate in blood stasis model rats. Conclusion： Sailong bone Zaizao Wan has protective effect on cerebral ischemia and its mechanisms may be related to its antioxidant capacity and improvement of hemorrheology.