通心络胶囊联合阿托伐他汀预处理对脑缺血再灌注损伤大鼠的保护作用  

Protective effect of Tongxinluo Capsule combined with atorvastatin preconditioning on cerebral ischemia-reperfusion injury in rats

作　　者：袁星宝 戴世杰 郑娅 Yuan Xingbao;Dai Shijie;Zheng Ya(Department of Pharmacy,Shaoing Second Hospital,Shaoring 312099,Zhejiang Province,China)

机构地区：[1]绍兴第二医院药剂科,312099 [2]杭州医学院药学院 [3]宁波市康复医院老年康复科

出　　处：《中华老年心脑血管病杂志》2023年第9期983-987,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：浙江省中医药科技计划项目(2020ZB230)。

摘　　要：目的探究通心络胶囊联合阿托伐他汀对脑缺血再灌注(CIRI)大鼠的神经保护作用及机制。方法30只SD大鼠随机分为假手术组、模型组、通心络胶囊预处理组[1 g/(kg·d)]、阿托伐他汀预处理组[10 mg/(kg·d)]、联合预处理组[1 g/(kg·d)通心络胶囊+10 mg/(kg·d)阿托伐他汀],每组6只,灌胃给药5 d后,大鼠造模后24 h、48 h、72 h测定大鼠贴纸去除时间,采用改良神经功能缺损评分(mNSS)。TTC染色、苏木精-伊红染色、TUNEL染色观察大鼠脑部梗死体积、病理变化及细胞凋亡情况;ELISA检测大鼠血清白细胞介素(IL)-1β、IL-6、TNF-α含量,黄嘌呤氧化酶法和硫代巴比妥酸法分别测定脑组织超氧化物歧化酶(SOD)活性和丙二醛水平,Western blot检测脑组织半胱氨酸天冬氨酸蛋白酶3(Caspase-3)、活化Caspase-3、B淋巴细胞瘤2基因(Bcl-2)、脑源性神经营养因子(BDNF)、血管内皮生长因子(VEGF)、神经生长因子(NGF)蛋白表达。结果通心络胶囊预处理组和阿托伐他汀预处理组造模后48 h、72 h贴纸去除时间、mNSS、脑梗死体积、血清IL-1β、IL-6及脑组织活化Caspase-3蛋白表达低于模型组(P<0.05),通心络胶囊预处理组和阿托伐他汀预处理组BDNF、VEDF、NGF蛋白表达明显高于模型组(1.78±0.20、1.92±0.21 vs 1.36±0.13,1.49±0.17、1.60±0.18 vs 0.76±0.08,3.08±0.32、3.22±0.34 vs 2.37±0.27,P<0.05,P<0.01)。联合预处理组造模后48 h、72 h贴纸去除时间、mNSS、脑梗死体积、血清IL-1β、TNF-α、IL-6、脑组织丙二醛水平级及活化Caspase-3蛋白表达明显低于通心络胶囊预处理组和阿托伐他汀预处理组(P<0.05,P<0.01),联合预处理组BDNF、VEDF、NGF蛋白表达明显高于通心络胶囊预处理组和阿托伐他汀预处理组(2.51±0.30 vs 1.78±0.20、1.92±0.21,2.92±0.31 vs 1.49±0.17、1.60±0.18,4.13±0.41 vs 3.08±0.32、3.22±0.34,P<0.05,P<0.01)。结论通心络胶囊联合阿托伐他汀对CIRI大鼠的神经保护作用效果�Objective To explore the neuroprotective effect and underlying mechanism of TXL Capsule combined with atorvastatin on rats with CIRI.Methods Thirty SD rats were randomly divided into sham group,model group,pre-TXL group[1 g/(kg·d)],pre-atorvastatin group[10 mg/(kg·d)],and combined pretreatment group(as above doses),6 in each group.All drugs were given by intragastric administration for 5 d.Adhesive removal test and mNSS were performed and evaluated in 24,48 and 72 h after modeling.TTC staining,HE staining and TUNEL staining were used to observe the infarct volume,pathological changes and cell apoptosis in brain tissue.ELISA was employed to detect the serum contents of IL-1β,IL-6 and TNF-α,xanthine oxidase and thiobarbituric acid assays were conducted to measure SOD activity and MDA content in brain tissue,and Western blotting was applied to detect the expression of Caspase-3,cleaved Caspase-3,Bcl-2,BDNF,VEGF and NGF in brain tissue.Results Compared to the model group,the pre-TXL group and pre-atorvastatin group showed remarkably shorten sticker removal time and lower mNSS in 48 and 72 h after modeling,decreased cerebral infarction volume,reduced serum contents of IL-1βand IL-6 and protein level of brain cleaved Caspase-3(P<0.05),as well as remarkably increased protein levels of BDNF,VEGF and NGF(1.78±0.20 and 1.92±0.21 vs 1.36±0.13,1.49±0.17 and 1.60±0.18 vs 0.76±0.08,3.08±0.32 and 3.22±0.34 vs 2.37±0.27,P<0.05,P<0.01).In 48 h and 72 h after modeling,the combined pretreatment group had remarkably shorten sticker removal time,lower mNSS,reduced cerebral infarction volume,decreased serum levels of IL-1β,TNF-αand IL-6 and brain MDA content as well as protein level of cleaved Caspase-3 when compared with the pre-TXL group and the pre-atorvastatin group(P<0.05,P<0.01).In 48 h and 72 h after modeling,the combined pretreatment group showed significantly higher expression levels of BDNF,VEDF and NGF than the pre-TXL group and pre-atorvastatin group(2.51±0.30 vs 1.78±0.20 and 1.92±0.21,2.92±0.31 vs 1.4

关 键 词：通心络胶囊 阿托伐他汀 脑缺血 再灌注损伤 神经保护 

分 类 号：R743[医药卫生—神经病学与精神病学]