阿托伐他汀预处理对大鼠脑缺血再灌注损伤的保护作用及炎症机制  

Protective effect and inflammatory mechanism of atorvastatin preconditioning on cerebral ischemia reperfusion injury in rats

作　　者：杨晓炜[1] 刘凤海[1] 崔新宇[1] 石文秀[1] 王锦涛 姚立岩[1] YANG Xiaowei;LIU Fenghai;CUI Xinyu;SHI Wenxiu;WANG Jintao;YAO Liyan(School of Public Health,Mudanjiang Medical College,Mudanjiang 157011,China)

机构地区：[1]牡丹江医学院公共卫生学院,黑龙江牡丹江157011

出　　处：《中国实用神经疾病杂志》2020年第15期1289-1294,共6页Chinese Journal of Practical Nervous Diseases

基　　金：黑龙江省卫生计生委科研课题(编号:2018157);牡丹江市科学技术计划项目(编号:z2018s056);黑龙江省省属高等学校基本科研业务费科研项目(编号:2018-KYYWFMY-0022)。

摘　　要：目的探讨阿托伐他汀预处理对大鼠脑缺血再灌注损伤的神经保护作用及其炎症机制。方法45只健康雄性SD大鼠按照随机数字表法分为假手术组、模型组和预处理组,每组15只。预处理组每日给予阿托伐他汀10 mg/(kg·d)灌胃,其余2组每日等体积生理盐水灌胃,共干预2周。末次灌胃24h模型组和预处理组均制备大鼠脑缺血再灌注损伤模型,假手术组仅分离血管不插入线栓。再灌注后2 h、6 h、12 h、24 h、48 h、72 h行神经功能评分并收集外周血,术后72 h处死大鼠,采集脑组织,采用2,3,5-氯化三苯基四氮唑(TTC)染色法检测脑梗死体积;采用ELISA检测各时点血清及72 h脑中TNF-α、NF-κB的表达。RT-PCR检测脑中TRL4、NF-κB mRNA表达。结果神经评分及TTC结果显示,模型组神经评分及脑梗死体积最大,预处理组神经评分及梗死体积显著减小(P<0.05)。ELISA结果显示,与假手术组比较,模型组和预处理组大鼠血清及脑TNF-α、NF-κB表达升高(P<0.05);与模型组比较,预处理组大鼠血清及脑组织TNF-α、NF-κB表达下降(P<0.05)。RT-PCR检测结果显示,与模型组比较,预处理组大鼠脑组织TRL4、NF-κB mRNA表达下降(P<0.05)。结论阿托伐他汀可改善大鼠脑缺血再灌注后神经功能损伤,减小梗死体积。其保护机制可能与下调TLR4/NF-κB信号转导通路进而降低炎症因子TNF-α的释放有关。Objective To investigate the neuroprotective effect of atorvastatin preconditioning on cerebral ischemia reperfusion injury in rats and its inflammatory mechanism.Methods 45 healthy male SD rats were randomly divided into sham operation group,model group and preconditioning group according to the random number table method,with 15 rats in each group.The pretreatment group was given atorvastatin 10mg/(kg·d)daily by gavage,and the other two groups were given normal saline daily by gavage,with a total intervention of 2 weeks.Rat cerebral ischemia-reperfusion injury models were prepared in both the model group and the preconditioning group after the last gavage for 24h,and only the blood vessels were separated without inserting thread plug in the sham operation group.After reperfusion,neurological function was scored and peripheral blood was collected at 2h,6h,12h,24h,48h and 72h.Rats were sacrificed and brain tissue was collected at 72h postoperatively.Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolium chloride(TTC)staining method.The expression of TNF-α,NF-κB in serum and brain at each time point was determined by ELISA.Expression of TRL4 and NF-κB mRNA in the brain was detected by RT-PCR.Results the results of nerve score and TTC showed that the nerve score and cerebral infarction volume were the largest in the model group,and the nerve score and infarction volume were significantly reduced in the pretreatment group(P<0.05).ELISA results showed that serum and brain TNF-α,NF-κB levels were increased in the model group and the preconditioning group compared with the sham group(P<0.05).Compared with the model group,TNF-α,NF-κB expression in serum and brain tissue of rats in the pretreatment group decreased(P<0.05).RT-PCR results showed that the mRNA expressions of TRL4 and NF-κB in the pretreated group decreased compared with the model group(P<0.05).Conclusion atorvastatin can improve the neurological function of rats after cerebral ischemia reperfusion and reduce the infarct volume.The pr

关 键 词：阿托伐他汀 脑缺血再灌注 TNF-α TRL4 NF-ΚB 

分 类 号：R-332[医药卫生]