摘要
目的研究吡格列酮改善糖尿病大鼠认知功能障碍的作用及其机制。方法将20只SD大鼠腹腔注射链脲霉素(60 mg/kg)建立1型糖尿病模型,随机分为糖尿病组(DM)、吡格列酮组[DM+PI,10 mg/(kg·d)],同龄大鼠10只作为正常对照组(Cont),连续灌胃给药8周后,采用Morris水迷宫评价其认知功能,取大脑颞叶皮质和海马进行以下指标测定:葡萄糖氧化酶法检测血糖水平,荧光分光光度法检测BACE1活性、AGEs水平,Western blot法检测BACE1、PPAR-γ、RAGE、COX2及iNOS蛋白表达,ELISA法检测TNF-α、IL-1β水平。结果与Cont组相比,DM组大鼠的学习记忆能力受损,海马CA1和CA3区神经元受损,血糖水平明显增加,长期给予吡格列酮改善了糖尿病大鼠以上指标的变化,差异有统计学意义(P<0.05或P<0.01)。吡格列酮对糖尿病大鼠体重没有明显影响。与Cont组相比,DM组大鼠大脑颞叶皮质和海马中BACE1酶活性、蛋白表达水平,AGEs、RAGE蛋白水平,炎症因子iNOS、TNF-α及IL-1β水平均明显增加,而PPAR-γ蛋白水平明显降低,差异有统计学意义(P<0.05或P<0.01)。经PI干预后,DM大鼠大脑颞叶皮质和海马中以上指标得到了明显的改善(P<0.05或P<0.01)。结论吡格列酮可改善1型糖尿病大鼠认知功能障碍,这与下调糖尿病状态下脑内BACE1,抑制AGEs/RAGE轴及炎症反应有关。
Objective To investigate the effects of pioglitazone on diabetic cognitive dysfunction and potential mechanisms.Methods Twenty SD rats were intraperitoneically injected with streptozotocin(60 mg/kg)to establish the model of type 1 diabetes,which was randomly divided into diabetes group(DM)and pioglitazone group[DM+PI,10 mg/(kg·d)],and ten age-matched rats were used as the normal control group(Cont).After continuous intragastric administration for 8 weeks,the cognitive perforamnce was evaluated by Morris water maze,and the temporal cortex and hippocampus were obtained to evaluate the following index:the blood glucose levels were detected by glucose oxidase assay,the activity ofβ-amyloid precursor protein cleaving enzyme 1(BACE1)and advanced glycation endproducts(AGEs)were measured by fluorescence spectrophotometry,the protein exression of BACE1,peroxisome proliferator-activated receptorγ(PPAR-γ),AGEs receptor(RAGE),and nitric oxide synthase(iNOS)were detected by Western blotting.Blood was obtained for the evaluation of the levels of TNF-αand IL-1βusing ELISA.Results Compared with Cont group,diabetic rats showed declined ability in learning and memory,damaged neurons in the hippocampus CA1 and CA3 area,decreased body weight,elevated blood glucose levels,and the difference was statistically significant(P<0.05 or P<0.01).Chronic PI treatment significantly improved changes in the above index.However,PI had no obvious effect on the body weight of diabetic rats.Moreover,there were significantly increases in activity,and protein levels of BACE1,AGEs level,protein expression of RAGE and iNOS in the brain,TNF-αand IL-1βlevel in serum(P<0.05 or P<0.01),while decrease in the PPAR-γprotein level in the brain of diabetic rats.PI treatment markedly reversed the above indexes changes(P<0.05 or P<0.01).Conclusion These findings demonstrated that ibuprofen markedly ameliorated diabetic cognitive dysfunction,potentially reflecting the down-regulation of BACE1,the suppression of the AGE/RAGE axis,and the anti-inflammation i
作者
朱霞
刘海燕
张亮
ZHU Xia;LIU Hai-yan;ZHANG Liang(Xuzhou Medical University,Xuzhou,Jiangsu 221004,China.)
出处
《中国处方药》
2020年第10期11-14,共4页
Journal of China Prescription Drug
基金
江苏省高校自然科学基金面上项目(18KJB310018)。
