摘要
目的:心血管并发症是糖尿病患者发病和死亡的主要原因。本文旨在探索莫诺苷对糖尿病大鼠缺血再灌注损伤的影响及其机制。方法:利用高糖饮食联合链脲佐菌素(STZ)诱导糖尿病大鼠模型。冠状动脉结扎术建立缺血再灌注模型。糖尿病大鼠随机分为4组:对照组(DM);对照加药组(DM+莫诺苷);模型组(I/R+DM);加药组(I/R+DM+莫诺苷)。苏木素伊红(HE)染色分析组织病理学变化。ELISA检测炎症因子TNF-α、IL-6、IL-10水平和氧化应激指标SOD和MDA水平。蛋白印迹检测肌红蛋白(Mb)、肌酸激酶同工酶(CK-MB)、肌钙蛋白I(c Tn I)、AMPKα1、PGC-1α和GLUT4的表达。结果:与对照组相比,模型组平均动脉压(MAP)、心率(HR)和左心室收缩压(LVSP)明显降低,心肌梗死面积增大(P<0.05)。与模型组相比,加药组MAP、HR和LVSP明显升高,心肌梗死面积明显变小(P<0.05)。同时,莫诺苷可改善糖尿病大鼠缺血再灌注导致的心肌组织病变。模型组Mb、CK-MB和c Tn I表达明显高于对照组(P<0.05)。加药组Mb,CK-MB和c Tn I表达明显低于模型组(P<0.05)。与对照组相比,模型组TNF-α和IL-6水平明显升高,IL-10水平明显下降(P<0.05)。与模型组相比,加药组TNF-α和IL-6水平明显降低,IL-10水平明显上升(P<0.05)。而且,模型组SOD水平明显低于对照组,MDA水平明显高于对照组(P<0.05)。与模型组相比,加药组SOD水平升高,MDA水平降低(P<0.05)。另外,模型组AMPKα1、PGC-1α和GLUT4的表达明显低于对照组(P<0.05)。加药组AMPKα1、PGC-1α和GLUT4的表达明显高于模型组(P<0.05)。结论:莫诺苷通过激活AMPKα/PGC-1α/GLUT4通路减轻糖尿病大鼠缺血再灌注损伤。
Objective：Cardiovascular complication is the primary cause of morbidity and mortality amongst the diabetic patients. This study aims to explore the effect of morroniside on the ischemia/reperfusion（ I/R） injury in diabetic rats. Methods：The diabetic rat model was induced by high glucose-diet and streptozocin. The I/R model was performed by coronary artery ligation. Diabetic rats were randomly divided into four groups：control group（ DM）;DM ＋ morroniside;model group（ I/R ＋ DM）;treatment group（ I/R ＋DM＋ morroniside）. Histopathological changes were measured by hematoxylin-eosin（ HE） staining. The levels of TNF-α,IL-6,IL-10,SOD and MDA were detected by ELISA. The expression of myoglobin（ Mb）,creatine kinase-MB（ CK-MB）,troponin-I（ c Tn I）,AMPKα1,PGC-1α and GLUT4 was tested through Western blot. Results：Compared with control group,the levels of mean arterial pressure（ MAP）,heart rate（ HR） and left ventricular systolic pressure（ LVSP） in model group were decreased with enhancive myocardial infraction area（ P〈0. 05）. Compared with model group,the levels of MAP,HR and LVSP in treatment group were elevated with declined myocardial infraction area（ P〈0. 05）. At the same time,the histopathological changes-induced by I/R were ameliorated by morroniside in diabetic rats. The expression of Mb,CK-MB and c Tn I in model group was higher than control group（ P〈0. 05）. The expression of Mb,CK-MB and c Tn I in treatment group was lower than model group（ P〈0. 05）. Compared with control group,the levels of TNF-α and IL-6 were increased with decreased level of IL-10（ P〈0. 05）. Compared with model group,the levels of TNF-α and IL-6 in treatment group were attenuated with enhanced level of IL-10（ P〈0. 05）. Moreover,the level of SOD in model group was lower than control group and the level of MDA in model group was higher than control group（ P〈0. 05）. Compared with model group,the level of SOD in treatment group was raised with reduced
作者
李霞
张铁军
封亚丽
LI Xia;ZHANG Tie-Jun;FENG Ya-Li(Department of Cardiology,Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050011,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2018年第7期990-995,共6页
Chinese Journal of Immunology
基金
河北省自然基金项目(No.H2015423064)
