摘要
目的探究鼠李黄素(Rhamnetin)保护糖尿病脑缺血再灌注大鼠脑损伤的可能机制。方法构建糖尿病大鼠模型,以线栓法建立脑缺血再灌注,予以50、100及200 mg/kg Rhamnetin灌胃,给药14 d后检测脑组织含水率、脑指数、细胞凋亡、血清炎性因子、凋亡及炎性反应标志物、Notch1及P38丝裂原活化蛋白激酶(P38 MAPK)蛋白表达。并添加Notch1激活剂Jagged1,观测各组Notch1、P38 MAPK蛋白表达。结果Rhamnetin中、高剂量干预后,大鼠跳台错误次数、脑指数、脑组织含水率、细胞凋亡率、IL-6、IL-1β、TNF-α、cleaved caspase-3/caspase-3、cleaved caspase-9/caspase-9、p-Notch1/Notch1及p-P38 MAPK/P38 MAPK减少,进入新异臂次数和IL-10增加(P<0.05);且Rhamnetin可抑制Jagged1对Notch1-P38 MAPK信号轴的激活(P<0.05)。结论鼠李黄素可保护糖尿病脑缺血再灌注大鼠脑组织损伤,可能与下调Notch1-P38 MAPK信号轴,减轻炎性反应有关。
Objective To explore the possible mechanism of rhamnetin on protecting brain damage in rats with diabetes mellitus(DM)undergoing cerebral ischemia-reperfusion(CI/R).Methods The model of DM rats was constructed,and CI/R was prepared by suture-occluded method.They were administered intragastrically with rhamnetin(50,100,200 mg/kg).The brain water content,brain index,cell apoptosis,serum inflammatory factors,markers for cell apoptosis and inflammatory response,expression levels of Notch1 and P38 mitogen-activated protein kinase(P38 MAPK)proteins were detected 14 days after administration.Notch1 activator Jagged1 was applied to observe the changes of expression levels of Notch1 and P38 MAPK proteins.Results After intervention with medium-and high-doses of rhamnetin,the number of error times in step-down test,the brain index and brain water content,the apoptosis rate,the levels of IL-6,IL-1β,TNF-α,and the expression levels of cleaved caspase-3/caspase-3,cleaved caspase-9/caspase-9,p-Notch1/Notch1 and p-P38 MAPK/P38 MAPK were decreased,while the number of times that the rat entering extraneous arms and the level of IL-10 were increased(P<0.05).Rhamnetin could inhibit the Jagged1 induced activation of Notch1-p38 MAPK signaling(P<0.05).Conclusion Rhamnetin can protect DM rats undergoing CI/R from brain tissue damage,its mechanism may be related to the alleviation of inflammatory response through down-regulation of Notch1-p38 MAPK signaling.
作者
张萍
苟芳
任嵘
ZHANG Ping;GOU Fang;REN Rong(Department of Endocrinology,Guangyuan Central Hospital,Guangyuan,Sichuan,628000,China)
出处
《医学分子生物学杂志》
CAS
2023年第2期166-172,共7页
Journal of Medical Molecular Biology
