摘要
目的探究右美托咪定(DEX)对缺血性卒中(IS)大鼠的保护作用及其机制。方法选择40只健康雄性SD大鼠,随机分为假手术组、IS组、DEX-低剂量组(低剂量组,DEX6mg/kg)和DEX-高剂量组(高剂量组,DEX12 mg/kg),每组10只。采用线栓法阻塞大脑中动脉血流构建IS模型,进行神经功能评分。慢病毒载体转染构建过表达Rho相关蛋白激酶(ROCK)2蛋白的SH-SY5Y细胞株,分为对照2组,糖氧剥夺(OGN)2组,DEX2组(n=6),DEX2组100ng/mlDEX预给药后,3组构建OGN模型,采用流式细胞仪检测藻红蛋白(PE)、异硫氰酸荧光素(FITC)双阳细胞比例。结果与假手术组比较,IS组大鼠神经功能缺损评分明显升高[(9.90±3.93)分vs(0.30±0.48)分,P<0.05],与IS组比较,低剂量组和高剂量组大鼠神经功能缺损评分明显减少[(5.90±1.60)分vs(9.90±3.93)分,P<0.05;(4.00±1.70)分vs(9.90±3.93)分,P<0.05]。与假手术组比较,IS组脑梗死体积百分比、TUNEL阳性细胞数量、脑组织ROCK2、磷酸化p38(p-p38)、磷酸化细胞外信号调节激酶(ERK)1/2(p-ERK1/2)和B淋巴细胞瘤2相关蛋白(Bax)表达明显升高,Bcl-2表达明显降低(P<0.05)。与IS组比较,低剂量组和高剂量组脑梗死体积百分比、TUNEL染色阳性细胞数量、ROCK2、p-p38、p-ERK1/2和Bax表达明显降低,Bcl-2表达明显升高(P<0.05,P<0.05)。与对照2组比较,OGN2组PE/FITC双阳性细胞比例明显升高(P<0.05);OGN2组与DEX2组PE/FITC双阳性细胞比例比较,差异无统计学意义(P>0.05)。结论DEX可能通过抑制ROCK2/p38丝裂原活化蛋白激酶通路减轻神经元凋亡,对IS具有保护作用。
Objective To explore the protective effect and mechanism of dexmedetomidine(DEX)on rats with ischemic stroke(IS).Methods Forty healthy male SD rats were randomly divided into sham group,IS group(intraluminal thread model of middle cerebral artery occlusion),and low-and high-DEX groups(6 and 12 mg/kg),with 10 animals in each group.Neurological score was evaluated.Cell stroke model in vitro was constructed by oxygen/glucose deprivation(OGN).SH-SY5Y cells overexpressing ROCK2 protein was constructed with lentiviral vector transfection.The cells were divided into control 2,OGN 2 and DEX 2 groups(n=6).Then,the effect of 100 ng/ml DEX on cell apoptosis with flow cytometry with PE and FITC double staining.ResultsThe neurological deficit score was significantly higher in the IS group than the sham group(9.90±3.93 vs 0.30±0.48,P<0.05),and low-and high-dose DEX treatment reduced the score when compared with that of the IS group(5.90±1.60 and 4.00±1.70 vs 9.90±3.93,both P<0.05).Compared with the sham group,the percentage of infarction volume,number of TUNEL positive cells,and expression levels of ROCK2,p-p38,p-ERK1/2 and Bax in brain tissue were significantly increased,while the level of Bcl-2 was obviously reduced in the IS group(P<0.05).While,low-and high-dose DEX treatment notably reversed above phenomena when compared with these in the IS group(P<0.05,P<0.05)There were more PE and FITC double positive cells in the OGN2 group than the control2 group(P<0.05),but no such difference was seen between the OGN2 group and the DEX2 group(P>0.05).Conclusion DEX may alleviate neuronal apoptosis by inhibiting the ROCK2/p38/MAPK pathway,and thereby exert a protective effect on IS.
作者
葛亮
张鹏
孔令国
范泉龙
童茜
李娜
韩旭东
Ge Liang;Zhang Peng;Kong Lingguo;Fan Quanlong;Tong Qian;Li Na;Han Xudong(Department of Anesthesiology,Gansu Provincial Maternal and Child Health Hospital,Lanzhou 730050,Gansu Province,China)
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2023年第7期756-760,共5页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
甘肃省自然科学基金(20JR10RA423)。
关键词
卒中
右美托咪啶
梗死
大脑中动脉
细胞凋亡
stroke
dexmedetomidine
infarction,middee cerebral artery
apoptosis
