阿托伐他汀对大鼠脑缺血再灌注损伤的保护作用及炎症机制Protective effect of atorvastatin on cerebral ischemia-reperfusion injury in rats and its inflammatory mechanism
杨晓炜;姚立岩;李海红;崔新宇;刘凤海;
摘要(Abstract):
目的通过使用不同剂量阿托伐他汀进行预处理再制备脑缺血再灌注模型,观察阿托伐他汀对缺血性脑卒中的保护作用并初探其炎症保护机制。方法将健康雄性SD大鼠随机分为:假手术组、模型组、不同剂量阿托伐他汀组A组:5 mg/(kg·d)、B组:10 mg/(kg·d)、C组:15 mg/(kg·d)、D组:20 mg/(kg·d)。每组按再灌注不同时间点分为4个亚组。模型组和阿托伐他汀组采用线栓法制备脑缺血再灌注模型,假手术组仅暴露血管不插线栓。参照Zea-Longa 5分制评分标准进行神经功能缺损评分;2%氯化三苯四唑啉(TTC)染色测量脑梗死体积;ELISA法检测hs-CRP、TNF-α和IL-10的表达。结果 (1)神经功能缺损评分:假手术组神经功能正常,模型组及各剂量组均有不同程度神经损伤,再灌注3 h及6 h,仅最高剂量阿托伐他汀组较模型组降低(P<0.05);再灌注12 h和24 h各剂量组较模型组神经评分呈剂量依赖性降低(P<0.05)。(2)脑梗死体积比较:再灌注3 h,最高剂量组与模型组比较梗死体积减小(P<0.05),再灌注6 h、12 h、24 h与模型组比较各组随剂量增加梗死体积减小(P<0.05)。(3)血清炎症因子测定:再灌注6 h、12 h、24 h模型组较假手术组hs-CRP升高,阿托伐他汀组较模型组hs-CRP降低(P<0.05),且呈剂量依赖性;各时间点模型组较假手术组TNF-α均升高(P<0.05),同一时点阿托伐他汀组较模型组TNF-α减少(P<0.05);再灌注6 h、12 h、24 h模型组较假手术组IL-10升高,与模型组比较,随阿托伐他汀剂量增加IL-10升高(P<0.05)。结论 (1)阿托伐他汀能减轻大鼠局灶性脑缺血再灌注的损伤,减轻神经功能缺损症状,缩小梗死体积,这种保护作用可能与其减少hs-CRP、TNF-α增加IL-10水平有关;(2)阿托伐他汀剂量越高在抗炎保护方面作用效果最好。
关键词(KeyWords): 阿托伐他汀;脑缺血再灌注;hs-CRP;TNF-α;IL-10
基金项目(Foundation): 黑龙江省卫生计生委科研课题(2018157);; 牡丹江市科学技术计划项目(z2018s056);; 黑龙江省省属高等学校基本科研业务费科研项目(2018-KYYWFMY-0022)
作者(Authors): 杨晓炜;姚立岩;李海红;崔新宇;刘凤海;
DOI: 10.13799/j.cnki.mdjyxyxb.2021.02.002
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