低剂量阿司匹林对大鼠慢性脑缺血诱导的脑白质损伤保护作用的研究

The low doses of aspirin protect aganist white matter lesion induced by chronic cerebral ischemia in rats

目的:探讨低剂量阿司匹林对慢性脑缺血诱导的大鼠脑白质损伤(white matter lesion,WML)的保护作用。方法:成年雄性SD大鼠20只,随机分为正常组、WML模型对照组、1 mg/kg/d阿司匹林处理组(ASA1)、10 mg/kg/d阿司匹林处理组(ASA10),每组5只。以双侧永久性颈总动脉结扎造成大鼠慢性脑缺血脑白质损伤。阿司匹林处理组腹腔注射不同剂量阿司匹林,连续30 d。采用卢卡斯快蓝(LFB)染色法检测胼胝体白质的形态,DiI示踪法检测轴突的损伤程度,Western Blot法检测胼胝体部位的髓鞘碱性蛋白(Myelin basic protein,MBP)和环核苷酸磷酸二酯酶(2’,3’-cyclic nucleotid3 phosphodiesterase,CNPase)的表达变化。结果:LFB染色显示:与正常组相比,WML对照组胼胝体髓鞘变稀疏,LFB染色变浅(P<0.05)。DiI染色显示:胼胝体轴突损伤明显,轴突延伸变短(P<0.05)。Western Blot显示:模型对照组胼胝体部位MBP和CNPase的表达显著降低(P<0.05)。然而,低剂量阿司匹林(1 mg/kg/d和10 mg/kg/d)可明显降低髓鞘损伤以及升高MBP和CNPase的表达(P<0.05)。但两个剂量组间差异无统计学意义。结论:大鼠脑白质损伤后给予低剂量的阿司匹林具有髓鞘保护的作用。

Objective： To investigate the protective effects of the low doses of aspirin on cerebral white matter lesion （WML） induced by chronic cerebral ischemia in rats . Methods： Twenty adult male Sprague-Dawley （SD） rats were randomly divided into normal group （normal, n = 5 ）, the WML model group （control, n = 5 ）, the model group treated with 1 mg/kg/d of aspirin （ASA1, n = 5 ）, the model group treated with 10 mg/kg/d of aspirin （ASA10, n = 5 ） . WML was induced by permanent bilateral common carotid artery occlusion. The rats in ASA1 or ASA10 group were received the different doses of aspirin for 30 days intraperitoneally. Lucas fast blue （LFB） staining was used to examine the morphology of the white matter in the corpus callosum. DiI trace method was used to observe the damage of axons. Western Blot were used for the detection of the expression of MBP and CNPase. Results： Compared with the normal group, LFB staining showed that in WML control group, the myelin in corpus callosum became thinner and weaker significantly （ P 〈 0. 05 ） ; DiI results revealed that the length of axons in corpus callosum across the midline was much shorter （P 〈 0. 05）. Western Blot showed that both MBP and CNPase expression were significantly reduced （P 〈 0. 05）. However, aspirin at low doses（ 1 mg/kg/d or 10 mg/kg/d ）could reduce the myelin damage and attenuate the decreased expression of MBP and CNPase induced by WML （ P 〈 0. 05 ）. Whereas, no significant differences were observed between the two groups. Conclusions： Low-doses aspirin may protect against WML- induced cerebral white matter lesions .