阿托伐他汀钙对非心源性缺血性脑卒中大鼠神经功能的影响

Effects of Atorvastatin Calcium on Nerve Function in Rats with Non-Cardiac Ischemic Stroke

目的:研究阿托伐他汀钙对非心源性缺血性脑卒中大鼠神经功能的影响及作用机理。方法:30只SD大鼠随机分为假手术组,模型组和阿托伐他汀组,每组各10只。对模型组和阿托伐他汀组大鼠建立非心源性缺血性脑卒中模型,阿托伐他汀组大鼠连续灌胃阿托伐他汀(1 mg·kg^(-1)·d^(-1))2 w,假手术组不阻塞颈内动脉,假手术组和模型组连续灌胃等体积0.9%氯化钠溶液。观察各组之间神经功能评估、脑组织病理变化、神经元凋亡、血清炎症因子(IL-6、TNF-α和IL-1β)水平等各项指标的差异,Western blotting法观察各组大鼠神经元凋亡相关蛋白TLR4、核转录因子NF-κB p65、p-IκB、Cleaved Caspase-3表达差异。结果:阿托伐他汀组神经功能缺陷评分、HE染色病理切片观察、细胞凋亡率、血清IL-6、TNF-α和IL-1β较模型组均明显改善(P<0.05)。Western blotting免疫印迹显示阿托伐他汀组大鼠TLR4、NF-κB p65、p-IκB、Cleaved Caspase-3较模型组明显下调(P<0.05)。结论:阿托伐他汀钙抑制TLR4和核转录因子NF-κB p65,通过该途径抑制非心源性缺血性脑卒中大鼠神经元细胞凋亡,改善神经功能障碍。

Objective:To study the effect of atorvastatin calcium on the neurological function of rats with non-cardiac ischemic stroke and its mechanism.Methods:Thirty SD rats were randomly divided into sham operation group,model group and atorvastatin group,with 10 in each group.Non-cardiac ischemic stroke models were established for rats in the model group and the atorvastatin group.The rats in the atorvastatin group were given continuous intragastric administration of atorvastatin(1 mg·kg^(-1)·d^(-1))for 2 w.For the sham operation group,the internal carotid artery was not blocked,and the sham operation group and the model group were given continuous intragastric administration of an equal volume of 0.9%sodium chloride solution.Observe the differences in various indicators such as neural function assessment,brain tissue pathological changes,neuronal apoptosis,and serum inflammatory factor levels(IL-6,TNF-αand IL-1β)among the groups,and Western blotting method to observe each group different expressions of rat neuronal apoptosis-related protein TLR4,nuclear transcription factor NF-κB p65,pIκB,Cleaved Caspase-3.Results:The neurological deficit score,HE staining pathological section observation,apoptosis rate,serum IL-6,TNF-αand IL-1βin the atorvastatin group were significantly improved compared with the model group(P<0.05).Western blotting showed that TLR4,NF-κB p65,p-IκB,and Cleaved Caspase-3 in the atorvastatin group were significantly down-regulated compared with the model group(P<0.05).Conclusion:Atorvastatin calcium inhibits TLR4 and nuclear transcription factor NF-κB p65,inhibits neuronal apoptosis in rats with non-cardiac ischemic stroke and improves neurological dysfunction through this pathway.