目的 探讨阿司匹林与尼莫地平预处理对脑缺血再灌注预后的影响。 方法 80只健康雄性SD大鼠随机分为假手术组、模型组、阿司匹林预处理组以及阿司匹林+尼莫地平预处理组,每组20只。以线栓法建立大鼠脑缺血再灌注模型,各组大鼠均于模型制作前5 d开始灌胃给药,连续用药5 d。假手术组和模型组给予生理盐水;阿司匹林预处理组灌胃给予阿司匹林50 mg/kg;阿司匹林+尼莫地平预处理组灌胃给予阿司匹林50 mg/kg+尼莫地平10 mg/kg。缺血2 h及再灌注24 h后比较各组神经功能缺失评分,用TTC染色测定脑梗死体积,用ELISA法测定脑组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、血栓素B2和6-酮-前列腺素1α的含量,并通过Real-time PCR检测大鼠Notch1、Jagged1和Hes1 mRNA表达以及通过Western blotting 检测Notch信号通路中Notch1、Jagged1及下游物质Hes1的表达水平。 结果 与模型组相比,阿司匹林+尼莫地平预处理组神经功能缺损评分显著降低(P<0.05),脑梗死体积显著缩小;阿司匹林预处理组和阿司匹林+尼莫地平预处理组脑组织SOD及6-酮-前列腺素1α显著高于模型组,MDA、血栓素B2及血栓素B2/6-酮-前列腺素1表达均低于模型组,且阿司匹林+尼莫地平预处理组变化更明显(P<0.05);阿司匹林预处理组和阿司匹林+尼莫地平预处理组的Notch1、Jagged1和Hes1 mRNA及蛋白表达水平显著低于模型组(P<0.05),且阿司匹林+尼莫地平预处理组表达量低于阿司匹林预处理组(P<0.05)。 结论 阿司匹林与尼莫地平两药合用时明显优于阿司匹林单独给药,可显著改善大鼠脑缺血再灌注损伤,这可能是通过影响Notch信号通路达到脑组织保护的作用。
Abstract
Objective To investigate the effects of the combination of aspirin and nimodipine preconditioning on the prognosis of cerebral ischemia-reperfusion. Methods Eighty healthy male SD rats were randomly divided into sham group, model group, aspirin preconditioning group and aspirin + nimodipine preconditioning group, with 20 rats in each group. The model of cerebral ischemia reperfusion was established. The rats in each group were given intragastric administration for 5 days before the model was established, and the drug was administered daily for 5 days. Sham group and model group were given normal saline; Aspirin preconditioning group was given 50 mg/kg aspirin; Aspirin + nimodipine preconditioning group was given 50 mg/kg aspirin and 10 mg/kg nimodipine. After 2 hours ischemia and 24 hours reperfusion, the animals were neurologically assessed, and then the volume of cerebral infarction was measured by TTC staining. The contents of superoxide dismutase (SOD), malondialdehyde (MDA), thromboxane B2, 6-keto-prostaglandin-1α in brain tissue were determined by ELISA. The mRNA expression of Notch1, Jagged1 and Hes1 in the brain tissues were detected by Real-time PCR, and the expressions of Jagged1 and Hes1, a downstream substance in Notch signaling pathway, were detected by Western blotting. Results The neurological deficit score of the aspirin+nimodipine pretreatment group was significantly lower than model group (P<0.05), and the cerebral infarction volume was significantly smaller than other groups. The SOD and 6-keto-prostaglandin 1 in the aspirin pretreatment group and the aspirin plus nimodipine pretreatment group were significantly higher than those in the model group, and the expressions of MDA, thromboxane B2 and thromboxane B2/6-keto-prostaglandin 1 were low. In the model group, the changes in the aspirin + nimodipine pretreatment group were more significant (P<0.05). The expression levels of Notch1, Jagged1 and Hes1 mRNA and protein in the aspirin pretreatment group and aspirin+nimodipine pretreatment group were significantly lower than those in the model group (P<0.05), and the expression level of aspirin+nimodipine pretreatment group was lower than that of aspirin pretreatment group (P<0.05). Conclusion The protective effect of aspirin plus nimodipine is superior to aspirin alone, which can significantly improve cerebral ischemia-reperfusion injury in rats, which may be exerted through influencing notch signaling pathway to achieve brain tissue protection.
关键词
阿司匹林 /
尼莫地平 /
脑缺血再灌注、 Notch信号通路 /
免疫印迹法 /
大鼠
Key words
Aspirin /
Nimodipine /
Cerebral ischemia reperfusion /
Notch signaling pathway /
Western blotting /
Rat
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基金
基金项目:甘肃省国际合作交流项目(编号:18YF1WA046);甘肃省自然科学基金(编号:18JR3RA060);中国科学院“西部青年学者项目”