Urocortin ameliorates diabetic cardiomyopathy in rats via the Akt/GSK-3β signaling pathway.
Urocortin ameliorates diabetic cardiomyopathy in rats via the Akt/GSK-3β signaling pathway.
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DOI：
10.3892/etm.2015.2211
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发表时间：
2015-03
影响因子：
2.7
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Liu X;Liu C;Zhang X;Zhao J;Xu J
尿皮质素已被证明对各种心血管疾病模型具有强大的保护作用。然而，尿皮质素在糖尿病性心肌病（DCM）预防中的作用和机制尚未阐明。本研究在糖尿病大鼠模型中研究尿皮质素对心功能障碍、纤维化、炎症及相关信号通路的影响。用链脲佐菌素腹腔注射诱导大鼠糖尿病（DM）。将糖尿病大鼠随机分为糖尿病对照组、尿皮质素组、尿皮质素+阿斯利康治疗组和尿皮质素+曲西瑞滨治疗组。所有实验均于诱导DM后16周进行，测定各组大鼠糖化血红蛋白（HbA1c）、肌酸磷酸激酶同工酶（CK-MB）、血浆脑钠肽（BNP）水平，以及心肌胶原体积分数（CVF）和左心室质量指数（LVWI）。此外，通过生化分析检测炎症因子，包括转化生长因子(TGF)-β1、结缔组织生长因子（CTGF）和相关蛋白，如Akt和糖原合成酶激酶(GSK)-3β的水平。糖尿病组大鼠BNP、CK-MB水平、TGF-β1、CTGF mRNA和蛋白表达水平、LVWI、CVF均高于对照组（P<0.05）。Akt和GSK-3β磷酸化水平降低（P<0.05）。值得注意的是，尿皮质素减轻了糖尿病大鼠的心肌功能障碍、心脏纤维化和心脏炎症。然而，尿皮质素对HbA1c水平没有影响。此外，给药后Akt和GSK-3β被抑制的磷酸化水平恢复。然而，用促肾上腺皮质激素释放因子受体2拮抗剂应激素治疗可消除尿皮质素的所有影响。Akt抑制剂Triciribine部分消除了尿皮质素对糖尿病大鼠心肌功能障碍、炎症和心脏纤维化的影响。这些结果表明，尿皮质素可能通过减轻纤维化和炎症在治疗DCM方面显示出巨大的治疗潜力。此外，Akt/GSK-3β信号通路可能部分参与介导这些作用。
Urocortin has been shown to exert powerful protective effects on various cardiovascular disease models. However, the role and mechanism of urocortin in protecting against diabetic cardiomyopathy (DCM) has not yet been elucidated. In the present study, the effects of urocortin on cardiac dysfunction, fibrosis, inflammation and the interrelated signaling pathways were investigated in a diabetic rat model. Diabetes mellitus (DM) was induced in the rats by intraperitoneal injection of streptozotocin. The diabetic rats were randomly divided into four groups: Diabetic control, urocortin, urocortin + astressin treatment and urocortin + triciribine treatment groups. All the experiments were conducted at 16 weeks following the induction of DM. The levels of glycosylated hemoglobin (HbA1c), creatine phosphokinase isoenzyme (CK-MB) and plasma brain natriuretic peptide (BNP), as well as the myocardial collagen volume fraction (CVF) and left ventricular mass index (LVWI), were measured. In addition, levels of inflammatory factors, including transforming growth factor (TGF)-β1, connective tissue growth factor (CTGF) and interrelated proteins, such as Akt and glycogen synthase kinase (GSK)-3β, were detected by biochemical analyses. In the diabetic group, the levels of BNP and CK-MB, as well as the mRNA and protein expression levels of TGF-β1 and CTGF, and the LVWI and CVF, were higher compared with the rats in the control group (P<0.05). This was accompanied by decreased Akt and GSK-3β phosphorylation (P<0.05). Notably, urocortin attenuated myocardial dysfunction, cardiac fibrosis and inflammation in the hearts of the diabetic rats. However, urocortin exhibited no effect on the level of HbA1c. In addition, the inhibited phosphorylation of Akt and GSK-3β was restored with urocortin administration. However, all the effects of urocortin were eliminated with treatment of the corticotropin releasing factor receptor 2 antagonist, astressin. Triciribine, an Akt inhibitor, partially eliminated the effects of urocortin on myocardial dysfunction, inflammation and cardiac fibrosis in the hearts of the diabetic rats. These results indicated that urocortin may exhibit great therapeutic potential in the treatment of DCM by attenuating fibrosis and inflammation. Furthermore, the Akt/GSK-3β signaling pathway may be partially involved in mediating these effects.
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DOI：
10.1161/circheartfailure.109.903450
发表时间：
2010-03
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Katare RG;Caporali A;Oikawa A;Meloni M;Emanueli C;Madeddu P
通讯作者：
Madeddu P
影响因子：
7.7
作者：
Huynh K;McMullen JR;Julius TL;Tan JW;Love JE;Cemerlang N;Kiriazis H;Du XJ;Ritchie RH
通讯作者：
Ritchie RH
影响因子：
8.2
作者：
Liu, Y.;Tanabe, K.;Baronnier, D.;Patel, S.;Woodgett, J.;Cras-Meneur, C.;Permutt, M. A.
通讯作者：
Permutt, M. A.
影响因子：
4.1
作者：
Liew, Hock-Kean;Hsu, Chih-Wei;Pang, Cheng-Yoong
通讯作者：
Pang, Cheng-Yoong
影响因子：
2.1
作者：
Liu, CN;Yang, C;Li, SN
通讯作者：
Li, SN