摘要
目的探究虫草素对糖尿病心肌病(diabetic cardiomyopathy,DCM)大鼠的干预效果及蛋白激酶B(protein kinase B,AKT)/糖原合成酶激酶3β(glycogen synthase kinase 3β,GSK3β)信号通路的调控作用。方法选择雄性SD大鼠80只构建DCM模型,随机分为模型组、虫草素组、AKT抑制剂组、虫草素+AKT抑制剂组,每组20只,构建DCM模型后分别给予相应干预。另取20只健康大鼠作为对照组。测定各组心功能指标[左心室射血分数(left ventricular ejection fraction,LVEF)、左心室短轴缩短分数(left ventricular fractional shortening,LVFS)、左心室收缩末期内径(left ventricular end systolic diameter,LVESD)、左心室舒张末期内径(left ventricular end diastolic diameter,LVEDD)];白细胞介素(interleukin,IL)-6、IL-1β、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、丙二醛及AKT/GSK3β信号通路相关蛋白表达。结果与对照组比较,模型组LVEF、LVFS、心肌组织SOD、GSH-Px、磷酸化-AKT(phosphorylated-AKT,p-AKT)/AKT、磷酸化-GSK3β(phosphorylated-GSK3β,p-GSK3β)/GSK3β蛋白表达显著降低,LVESD、LVEDD、心肌组织IL-6、IL-1β、TNF-α、丙二醛蛋白表达显著升高(P<0.05)。与模型组比较,虫草素组LVEF、LVFS、心肌组织SOD、GSH-Px、p-AKT/AKT、p-GSK3β/GSK3β蛋白表达显著升高,LVESD、LVEDD、心肌组织IL-6、IL-1β、TNF-α、丙二醛、Bax蛋白表达显著降低(P<0.05),AKT抑制剂组LVEF、LVFS、心肌组织SOD、GSH-Px、p-AKT/AKT、p-GSK3β/GSK3β蛋白表达显著降低,LVESD、LVEDD、心肌组织IL-6、IL-1β、TNF-α、丙二醛表达显著升高(P<0.05)。与虫草素组比较,虫草素+AKT抑制剂组LVEF、LVFS、心肌组织SOD、GSH-Px、p-AKT/AKT、p-GSK3β/GSK3β蛋白表达显著降低,LVESD、LVEDD、心肌组织IL-6、IL-1β、TNF-α、丙二醛表达显著升高(P<0.05)。与AKT抑制剂组比较,虫草素+AKT抑制剂组LVEF、LVFS显著升高[(61.29±5.61)%vs(39.28±4.12)%,(39.05±3.43)%vs(24.47±2.73)%,P<0.05],LVESD、LVEDD显著降低[(4.36±0.48)mm vs(6.97±0.69)mm,(6.07±0.61)mm vs(9.02±0.85)mm,P<0.05]。结论虫草素可能通过激活AKT/GSK3β信号通路改善DCM大鼠心功能、心肌损伤、炎症和氧化应激,并抑制心肌细胞凋亡。
Objective To investigate the intervention effect of cordycepin on DCM rats and its regulative effect on of AKT/GSK3βsignaling pathway.Methods A total of 80 male SD rats were randomly divided into model group,cordycepin group,AKT inhibitor group and cordycepin+AKT inhibitor group,with 20 rats in each group.After the establishment of DCM model,corresponding intervention was given to each group.Another 20 healthy rats served as control group.Cardiac function indicators(LVEF,LVFS,LVESD,LVEDD),levels of IL-6,IL-1β,TNF-α,SOD,GSH-Px and MAD,and expression of AKT/GSK3βsignaling pathway related proteins were determined and compared among the groups blotting.Results The model group had significantly lower LVEF and LVFS,decreased myocardial SOD and GSH-Px contents,and declined p-AKT/AKT and p-GSK3β/GSK3β,but increased LVESD and LVEDD and myocardial IL-6,IL-1β,TNF-αand MAD expression levels when compared with the control group(P<0.05).Cordycepin treatment obtained increased LVEF and LVFS and myocardial tissue SOD,GSH-Px,Bcl-2,p-AKT/AKT and p-GSK3β/GSK3βprotein expressions,and decreased LVESD and LVEDD and myocardial expression of IL-6,IL-1β,TNF-α,MAD and Bax than the model group(P<0.05),while AKT inhibitor reversed all the changes induced by modelling(P<0.05).Combination of cordycepin+AKT inhibitor resulted in lower LVEF,LVFS and myocardial SOD,GSH-Px,Bcl-2,p-AKT/AKT,p-GSK3β/GSK3βprotein levels,and increased LVESD,LVEDD and expressions of IL-6,IL-1β,TNF-α,MAD and Bax protein in myocardial tissue when compared with cordycepin group(P<0.05).And the combination also resulted in increases in LVEF and LVFS[(61.29±5.61)%vs(39.28±4.12)%,(39.05±3.43)%vs(24.47±2.73)%,P<0.05]and decreases in LVESD and LVEDD(4.36±0.48 mm vs 6.97±0.69 mm,6.07±0.61 mm vs 9.02±0.85mm,P<0.05)when compared with AKT inhibitor group.Conclusion Cordycepin improves cardiac function,myocardial injury,inflammation and oxidative stress in DCM rats probably by activating AKT/GSK3βsignaling pathway,and inhibits the apoptosis of cardiomyocyte.
作者
李丹
左淑萍
张守军
徐宝清
武海岗
李春苗
Li Dan;Zuo Shuping;Zhang Shoujun;Xu Baoqing;Wu Haigang;Li Chunmiao(Third Department of Cardiology,Tangshan Workers'Hospital,Tangshan 063003,Hebei Province,China)
出处
《中华老年心脑血管病杂志》
2025年第4期504-509,共6页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
河北省医学科学研究课题计划项目(20241492)。
