Urocortin对糖尿病心肌病的保护作用与Akt/GSK-3β信号通路的关系  

Protective effects of urocortin on diabetic cardiomyopathy and relationship via Akt/GSK-3β signaling pathway

作　　者：刘新宇 刘春娜 李思璇 郑晨 刘婉珠 LIU Xin-yu;LIU Chun-na;LI Si-xuan;ZHENG Chen;LIU Wan-zhu(Dept of Endocrinology, the First Affiliated Hospital, Jinzhou Liaoning 121001,China;Dept ofPharmacology,Jinzhou Medical University, Jinzhou Liaoning 121001,China)

机构地区：[1]锦州医科大学附属第一医院内分泌科,辽宁锦州121001 [2]锦州医科大学基础医学院药理学教研室,辽宁锦州121001

出　　处：《中国药理学通报》2019年第7期973-977,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81201037);辽宁省重点研发计划指导计划项目(No 2018225030)

摘　　要：目的 观察内分泌-血管活性肽Urocortin(UCN)对糖尿病心肌病(DCM)大鼠TGF-β1和CTGF的影响,研究UCN对DCM的保护作用及可能机制。方法 建立糖尿病(DM)模型,将大鼠分为5组:Control组、DCM组、UCN组、UCN+Astressin组、UCN+Triciribine组。饲养12周后处理4周,测定血糖、尿糖、尿量,以及血清TGF-β1、CTGF水平;观察心肌细胞形态学;测定心肌组织TGF-β1、CTGT、Akt、GSK-3β、p-Akt、p-GSK-3β的表达。结果 DM大鼠心肌形态学符合DCM改变,与Control组相比,DCM组血清与心肌组织TGF-β1、CTGF水平均增高,DCM组心肌组织p-Akt、p-GSK-3β均降低( P <0.05)。与DCM组相比,UCN组TGF-β1、CTGF水平均降低( P <0.05),Astressin和Triciribine均能阻断UCN的作用( P <0.05);UCN组p-Akt、p-GSK-3β表达增高( P <0.05),Astressin阻断UCN的作用( P <0.05)。结论 UCN对DCM的保护作用可能通过与CRH-R受体结合后,激活Akt/GSK-3β信号通路,下调炎症因子TGF-β1及CTGF的表达有关。Aim To observe the effects of UCN on TGF-β1 and CTGF in rats with DCM, and to explore the protective effects of UCN on DCM and its possible signaling pathway.Methods The rats were divided into five groups: control group, DCM group, UCN group, UCN+Astressin group, and UCN+Triciribine group.After12 weeks of feeding and 4 weeks of treatment, blood glucose, urinary sugar, urine volume and the levels of TGF-β1, CTGF in serum were determined, and the expression of TGF-β1, CTGF, Akt, GSK-3β, p-Akt and p-GSK-3β of cardiomyocytes were also determined.Results The myocardial HE staining in DM rats was consistent with DCM.The levels of TGF-β1 and CTGF in serum and myocardium of rats with DCM increased significantly, while the levels of p-Akt and p-GSK-3β in myocardium of rats with DCM decreased significantly ( P <0.05).The levels of TGF-β1 and CTGF in UCN group decreased, both astressin and triciribine could inhibit the role of UCN, and the expression of p-Akt and p-GSK-3β in myocardial cells in UCN group increased significantly, then astressin could inhibit the role of UCN ( P <0.01).Conclusions The protective effects of UCN on DCM might be related to the activation of Akt/GSK-3β signaling pathway after binding with CRH-R receptor, and then decreasing the expression of TGF-β1 and CTGF.

关 键 词：UROCORTIN 糖尿病心肌病 转化生长因子-β1 结缔组织生长因子 AKT 糖原合成酶激酶3Β 

分 类 号：R-332[医药卫生] R322.11