JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2017, Vol. 55 ›› Issue (10): 65-70.doi: 10.6040/j.issn.1671-7554.0.2016.1152

Previous Articles     Next Articles

Perindopril ameliorates cardiac dysfunction via Akt-FoxO1 pathway in diabetic cardiomyopathy

GONG Luwei, ZHOU Lizhen, SU Guohai   

  1. Department of Cardiology, Jinan Central Hospital, Affiliated to Shandong University, Jinan 250013, Shandong, China
  • Received:2016-09-13 Online:2017-10-10 Published:2017-10-10

PDF (PC)

38

Abstract: Objective To investigate the role and potential mechanism of perindopril on myocardial dysfunction in DCM(diabetic cardiomyopathy). Methods A total of 40 male Sprague-Dawley rats(100-120 g)were divided into 3 groups: control(n=10), DCM group(n=15)and DCM+perindopril group(n=15). The control group was fed with basal diet, while the DCM group and DCM+perindopril group were established as diabetic models. After the models were successfully established, the DCM group received intragastric normal saline, and DCM+perindopril group received intragastric perindopril 4 mg/(kg·d). The effect of perindopril on the rats cardiac function, myocardial apoptosis and fibrosis were observed. The protein expressions of p-Akt and p-FoxO1 were examined withWestern blotting. Results Compared with the control group, the DCM group exhibited severe left ventricular dysfunction, myocardial apoptosis and fibrosis, significantly increased p-FoxO1 expressio and decreased p-Akt protein expression(P<0.05). Compared with the DCM group, the DCM+perindopril group had better cardiac function and lower p-Akt protein expression(P<0.05). Conclusion Perindopril protects cardiac function by inhibiting myocardial apoptosis and fibrosis in diabetic rat svia Akt-FoxO1 pathway.

Key words: Perindopril, Cardiac function, Apoptosis, Fibrosis, Diabetic cardiomyopathy

CLC Number: 

  • R587.2
[1] Tarquini R, Lazzeri C, Pala L, et al. The diabetic cardiomyopathy[J]. Acta Diabetol, 2011, 48(3):173-181.
[2] Cal L, Li W, Wang G, et al. Hyperglycemia-induced apoptosis in mouse myocardium:mitochondrial cytochrome C-mediated caspase-3 activation pathway[J]. Diabetes, 2002, 51(6):1938-1948.
[3] Fiordaliso F, Li B, Latini R, et al. Myocytes death in streptozotocin-induced diabetes in rats is angiotensin II-dependent[J]. Lab Invest, 2000, 80(4):531-527.
[4] Sun JY, Zhai L, Li QL, et al. Effects of ACE inhibition on endothelial progenitor cell mobilization and prognosis after acute myocardial infarction in type 2 diabetic patients[J]. Clinics, 2013, 68(5):665-673.
[5] Devereux RB, Roman MJ, Paranicas M, et al. Impact of diabetes on cardiac structure and function:the strong heart study[J]. Circulation, 2000, 101(19):2271-2276.
[6] 赵航,冯景辉,吴秀萍.糖尿病心肌病发病机制的研究[J].国际心血管病杂志,2016, 43(1):16-18.
[7] 林雪,方理刚.糖尿病与心力衰竭[J].临床内科杂志,2016, 33(4):227-231.
[8] Asbun J, Villarreal FJ. The pathogenesis of myocardial fibrosis in the setting of diabetic cardiomyopathy[J].J Am CollCardiol, 2006, 47(4):693-700.
[9] 中华医学会心血管病学分会, 中华心血管病杂志编辑委员会. 血管紧张素转换酶抑制剂在心血管病中应用专家共识[J]. 中华心血管病杂志,2007,35(2):97-106. Chinese Society of Cardiology of Chinese Medical, Editorial board of Chinese Journal of Cardiology. Chinese expert consensus document on angiotensin converting enzyme inhibitors in cardiovascular diseases[J]. Chinese Journal of Cardiology, 2007, 35(2):97-106.
[10] Qu Z, Xu H, Tian Y. Effects of angiotensin-converting enzyme inhibition and bradykinin peptides in rats with myocardial infarction[J]. Int J Clin Exp Pathol, 2015, 8(3):3410-3417.
[11] Zhang JN, Geng Q, Chen XJ, et al. Alteration of endothelin system and calcium handling protein in left ventricles following drug treatment in dilated cardiomyopathy rats[J]. Acta Pharmacol Sin, 2003, 24(11):1099-1102.
[12] Wang CH, Verma S, Hsieh IC, et al. Enalapril increases ischemia-induced endothelial progenitor cell mobilization through manipulation of the CD26 system[J]. J Mol Cell Cardiol, 2006, 41(1):34-43.
[13] McConnell KJ, Humphries TL, Raebel MA, et al. Clinical pharmacy specialist implementation of lisinopril therapy in patients with coronary artery disease and diabetes mellitus[J]. Pharmacotherapy, 2003, 23(12):1564-1572.
[14] 李春霞, 黄宝群. 培哚普利与美托洛尔诊治糖尿病无症状心功能不全50例的临床效果观察[J]. 糖尿病新世界, 2014, 8(5):23.
[15] 钟惠菊, 周敏, 吴小英, 等. 培哚普利对STZ糖尿病大鼠心肌保护作用的实验研究[J].中国临床保健杂志, 2001, 4(2):106-109. ZHONG Huiju, ZHOU Min, WU Xiaoying, et al. An experimental study on the cardial protective effect of perindopril in diabetic rats[J]. J Clin Healthcare, 2001, 4(2):106-109.
[16] Gross DN, Wan M, Birnbaum MJ. The role of FOXO in the regulation of metabolism[J].Curr Diab Rep, 2009, 9(3):208-214.
[17] Kong X, Zhang L, Hua X, et al. Squamosamide derivative FLZ protects pancreatic β-Cells from glucotoxicity by stimulating Akt-FOXO1 pathway[J]. Diabetes Res, 2015:803986-803995. doi:10.1155/2015/803986.
[18] Puthanveetil P, Wan A, Rodrigues B. FoxO1 is crucial for sustaining cardiomyocyte metabolism and cell survival[J]. Cardiovasc Res, 2012, 97(3):393-403.
[19] Dharaneeswaran H, Abid MR, Yuan L, et al. FOXO1-mediated activation of Aktplays a critical role in vascular homeostasis[J]. Circ Res, 2014, 115(2):238-251.
[20] Battiprolu PK, Hojayev B, Jiang N, et al. Metabolic stress-induced activation of FoxO1 triggers diabetic cardiomyopathy in mice[J]. J Clin Invest, 2012, 122(3):1109-1118.
[21] Kitamura T, Nakae J, Kitamura Y, et al.The forkhead transcription factor Foxo1 links insulin signalingtoPdx1 regulation of pancreatic βcell growth[J]. J Clin Invest, 2002, 110(12):1839-1847.
[1] LU Xiang-Dong, YANG Wei, XU Guang-Meng, QU Yuan-Ming. Expression and role of PPAR-γin meningiomas and troglitazone induced meningiomas cell apoptosis in vitro [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 65-.
[2] ZHANG Liang, XU Min, ZHUANG Xianghua, LOU Fuchen, LOU Nengjun, LÜ Li, GUO Wenjuan, ZHENG Fengjie, CHEN Shihong. An investigation of endoplasmic reticulum stress and apoptosis in diabetic peripheral neuropathy [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(8): 13-17.
[3] YAN Fangying, SHAN Xiaolan, LI Jingyuan, ZHANG Jie, YAN Xuefang, YANG Yi, BU Peili. Pioglitazone ameliorates cardiac fibrosis induced by hypertension via regulating Sirt3 [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(5): 13-18.
[4] LI Rui, MA Weihong, REN Manyi, ZHAO Mengmeng, JIANG Shan, JU Yuanyuan, GUO Ying, SUN Zhaohui, SUI Shujian. Correlation between TWEAK and cardiac remodeling in essential hypertensive patients [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(5): 49-55.
[5] GUO Hehe, SUN Zhiqiang, LIU Yanjuan, LIU Yichen, LI Guang, ZHENG Fang. Norcantharidin influences the expression of Notch signal pathway in multiple myeloma U226 cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(3): 32-37.
[6] TAN Hong, MENG Nan, JIN Qun, SU Li, ZHANG Xiaxiao, CHEN Yingjian, HAO Zhe, LIU Xiaohong. Effects of different doses of perindopril on endothelial progenitor cells and systolic cardiac function in rabbits with acute myocardial infarction [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(2): 55-60.
[7] TU Yunhua, CHEN Liyuan, WANG Xi, ZHOU Ying, KANG Yingqian, XUE Yuecui, RONG Dongyun, YE Zhenyuan, CAO Yu. Effect of ar-turmerone derivatives on proliferation and apoptosis in human melanoma WM35 cells [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(2): 68-73.
[8] ZHAO Lu, JIAO Jun, ZHANG Teng, JIAO Xinlin, CUI Baoxia. Expression of LXRα in ovarian carcinoma and effects of T0901317 on SKOV3 cell line [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(1): 49-53.
[9] JIANG Yunshan, TAN Hong, LI Xiaoyan, SU Li, ZHANG Guoming, ZHANG Hongming, MENG Nan. Effects of perindopril on the expression of plasma miR-423-5p and cardiac function in patients with heart failure [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(8): 55-59.
[10] ZHAN Fengxia, DING Juan, MA Beilei, WANG Qian. Effects of estradiol on Th1 cell polarization and liver fibrosis [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(8): 64-68.
[11] ZHANG Kun, ZHAGN Xiaoguo, CUI Xingxing, CHEN Shijun. Expression of apoptosis-related genes in peripheral blood mononuclear cells of patients with HBV infection and the relationship with chronicity of hepatitis B [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(7): 38-42.
[12] JU Yuanyuan, REN Manyi, LI Rui, ZHAO Mengmeng, SUI Shujian. Tumor necrosis factor-like weak inducer of apoptosis promotes expression of matrix metalloproteinase 2 and collagen Ⅰ in rat cardiac fibroblasts via the ERK1/2 signaling pathway [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(5): 23-28.
[13] LI Hongzhi, LIU Jing, SONG Yan, CHI Lingyi, LIU Yuguang. Role of liraglutide in the repair of spinal cord injury [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(4): 1-5.
[14] XI Fuli, ZHANG Mei. Regulation of microRNA-34a on SH2B3 expression during cardiac fibrosis [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(2): 6-10.
[15] REN Baoxin, MA Yunfeng, LIU Dianwei, LI Zhuo, JIANG Yong. Effects of Wnt3a on neuronal autophagy and apoptosis in early brain injury after subarachnoid hemorrhage in rats [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(10): 11-15.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd