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作 者:万嘉洋 万海同[1] 何昱[1] 虞立[1] 杨洁红 周惠芬[1]
出 处:《中成药》2017年第11期2236-2242,共7页Chinese Traditional Patent Medicine
基 金:国家自然科学基金资助项目(81630105;81603531);浙江省自然科学基金资助项目(LZ17H270001);浙江省中医药管理局资助项目(2016ZZ010)
摘 要:目的探究活血康脑颗粒(黄芪、巴戟天、葛根等)对大鼠脑缺血再灌注损伤的保护作用。方法建立大鼠大脑中动脉栓塞(MCAO)模型,SD大鼠随机分为假手术组,模型组,阳性对照组,活血康脑颗粒低、中、高剂量组。测试神经功能评分,TTC染色计算脑梗死体积,酶联免疫吸附(ELISA)法检测超氧化物歧化酶(SOD)、丙二醛(MDA)、6-酮-前列腺素(6-keto-PGFlα)、血栓素B2(TXB2)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α),逆转录-聚合酶链反应(RT-PCR)法检测基质金属蛋白酶9(MMP-9)、细胞间黏附分子-1(ICAM-1)表达水平。为了观察活血康脑颗粒对血小板聚集功能的影响,全自动血凝分析仪分析凝血时间,ELISA法测定血浆组织型纤溶酶原激活物(t-PA)和抑制物(PAI)活性,全自动生化分析仪检测血液流变学指标。结果活血康脑颗粒能显著减少脑梗死体积,改善神经功能,降低MDA含有量,增加SOD活性;升高6-keto-PGF1α水平,降低TXB2含有量;减少IL-1β和TNF-α表达;抑制MMP-9、ICAM-1表达;延长白陶土部分凝血活酶时间(KPTT)、血浆凝血酶原时间(PT);升高t-PA活性,抑制PAI活性;降低全血黏度,提高红细胞变形能力。活血康脑颗粒每个剂量组的量效呈正相关。结论活血康脑颗粒可保护大鼠脑缺血再灌注损伤,其机制可能与抗自由基损伤、抗血栓、抗脑血管痉挛、改善脑血管通透性、抗炎、抗凝血、改善血液流变学异常变化有关。AIM To explore the protective effects of Huoxue Kangnao Granules(Astragali Radix,Morindae officinalis Radix,Puerariae lobatae Radix,etc.) on cerebral ischemia-reperfusion injury in rats. METHODS The rat model for middle cerebral artery occlusion(MCAO) was established,SD rats were randomly divided into sham operation group,model group,positive control group,Huoxue Kangnao Granules low-,middle-and highdose groups. Nerve function score was tested. Volume of cerebral infarction was calculated by TTC staining. SOD,MDA,6-keto-PGFlα,TXB2,IL-1β and TNF-α were detected by ELISA. The expression levels of MMP-9 and ICAM-1 were detected by RT-PCR. To observe the influence of Huoxue Kangnao Granules on platelet aggregative function,clotting time was analyzed by automatic blood coagulation analyzer,plasma T-PA and PAI activities were determined by ELISA,and hemorheology indices were detected by automatic biochemical analyzer. RESULTS Huoxue Kangnao Granules could significantly decrease cerebral infarction volume,improve nerve function,reduce MDA content,increase SOD activity; increase 6-keto-PGF1α level,reduce TXB2 content; decrease TNF-α and IL-1β expressions; inhibit MMP-9 and ICAM-1 expressions; extend KPTT and PT; elevate t-PA activity,inhibit PAI activity; decrease whole blood viscosity,enhance erythrocyte deformation ability. Each dosage group of Huoxue Kangnao Granules had a positive correlation between dose and response. CONCLUSION Huoxue Kangnao Granules can protect cerebral ischemia-reperfusion injury in rats,whose mechanisms may be related to anti-free radical injury,anti-thrombus,anti-cerebral vasospasm,improving cerebrovascular permeability,anti-inflammatory,anti-coagulation and improving abnormal changes of hemorheology.
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