机构地区:[1]湖北省大冶市人民医院神经内科,湖北大冶435100 [2]武汉大学中南医院药剂科,武汉430071
出 处:《中南药学》2016年第2期145-149,共5页Central South Pharmacy
基 金:湖北省黄石市医药卫生科研指导性项目(No.2014-20)
摘 要:目的观察黄腐酸钠对大鼠脑缺血再灌注损伤炎症反应的影响。方法 SD大鼠随机分为假手术组、模型组、黄腐酸钠50、100、150 mg组。黄腐酸钠术前灌胃3 d,2次·d-1。线栓法制作大鼠局灶性脑缺血再灌注损伤模型,缺血1.5 h再灌注24 h。术后对大鼠神经功能进行评分;TTC染色观察脑梗死体积;干湿重法测定脑含水量;分光光度法测定髓过氧化物酶(MPO)活性;伊文思兰(EB)法测定血脑屏障的损伤程度;ELISA法检测TNF-α和IL-1β的含量;Western blot法检测核抽提物中NF-κBp65蛋白的表达。结果 3个剂量的黄腐酸钠均能明显改善大鼠脑缺血再灌注损伤的神经缺陷症状,缩小脑梗死体积。与黄腐酸钠50 mg治疗组相比,黄腐酸钠100 mg治疗组更能改善大鼠神经缺陷评分和缩小脑梗死体积,2组之间差异具有统计学意义(P<0.05),但黄腐酸钠100 mg治疗组与黄腐酸钠150 mg治疗组之间差异无统计学意义。黄腐酸钠100 mg能明显降低缺血侧脑组织的含水量、EB含量及MPO活性;显著抑制TNF-α和IL-1β的表达并减少脑组织核抽提物中NF-κBp65的蛋白量(P<0.05)。结论黄腐酸钠能明显改善血脑屏障通透性、减轻脑水肿,减轻白细胞的浸润,降低缺血区脑组织中IL-1β与TNF-α的含量以及抑制NF-κBp65的活化,减轻脑缺血再灌注损伤的炎症反应,黄腐酸钠对脑缺血再灌注损伤具有保护作用。Objective To determine the effect of sodium fulvate on inflammatory reaction after cerebral ischemia/reperfusion(I/R) injury in rats. Methods SD rats were randomly divided into 5 groups: a sham-operated group, a control group, sodium fulvate 50, 100 and 150 mg groups. Sodium fulvate was administered twice daily intragastrically injection for 3 days before the operation. Focal cerebral ischemia/reperfusion model in rats was made by transient occlusion of the middle cerebral artery for 90 min followed by 24 h reperfusion. The neurological function was scored and the infarct volume was measured after the operation. Brain edema was measured with dry-wet weight. Myeloperox-idase activity was determined by spectrophotometer. The permeability of the blood brain barrier was evaluated by measurement of the Evans Blue content in the brain with spectrophotometer. The brain content of TNF-α and IL-1β were evaluated with ELISA method. The content of NF-κBp65 protein in the nuclear extracts was detected by Western blot. Results Compared with the model group, sodium fulvate(50, 100 and 150 mg) could improved the neurological function and decreased the infarct size. Compared with the 50 mg sodium fulvate group, the 100 mg sodium fulvate group better improved the neurological function and decreased the infarct size(P〈0.05). However, there was no significant difference between the 100 mg sodium fulvate group and the 150 mg sodium fulvate group in the neurological function and infarct size. Sodium fulvate(100 mg) reduced the permeability of blood brain barrier and brain water content, inhibited the myeloperox-idase activity, and decreased the content of TNF-α and IL-1β in brain tissue and the content of NF-κBp65 protein in the nuclear extracts significantly(P〈0.05). Conclusion Sodium fulvate can obviously improve the blood brain barrier permeability, reduce brain edema and the infiltration of leukocytes, reduce ischemic brain tissue TNF-α and IL-1β of the content and inhibit the activation of NF-κ
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