doi:10.3969/j.issn.1674-490X.2018.06.005

Abstract

Abstract: Objective To discuss whether liraglutide has protective effect on myocardial cell damage induced by hypoxia/reoxygenation(H/R)and its possible mechanism.Methods Myocardial cells of neonatal rats were cultured as the object of experiment, and the cells were divided into 5 groups: normal control group(Group A), pure H/R group(Group B), Liraglutide+H/R group(Group C), H/R+ Liraglutide+LY294002 group(Group D), and H/R+LY294002 group(Group E). In each group, n=8. Cell supernatant, the level of lactic dehydrogenase(LDH)and malondialdehyde(MDA), and superoxide dismutase(SOD)activity were detected respectively for the three groups. Double staining method of the flow cytometry was applied to detect apoptosis rate of myocardial cells in each group and the activity of Caspase-3. Results Compared with Group A, the level of LDH and MDA, apoptosis rate and Caspase-3 activity in Group B increased significantly, while SOD activity decreased. The differences had statistical significance(P<0.01). Compared with Group B, the level of LDH and MDA, apoptosis rate and Caspase-3 activity in Group C lowered, while SOD activity rose. The differences had statistical significance(P<0.01). Compared with Group C, the level of LDH and MDA, apoptosis rate and Caspase-3 activity in Group D rose, while SOD activity lowered. The differences had statistical significance(P<0.01). For the changes in the above indexes, the comparison between Group B and Group E had no statistical significance(P>0.05). Conclusion H/R damages myocardial cell, while liraglutide directly affects myocardial cells and may protect myocardial cells to certain degree through anti-oxidative stress damage, apoptosis inhibition and reduction of membrane permeability. PI3K pathway may be related to the anti-apoptosis effect and oxidative stress mechanism of liraglutide on myocardial cell.

Key words: Liraglutide, hypoxia/reoxygenation, myocardial cell, apoptosis, oxidative stress, phosphatidylinositol 3-kinases

CLC Number:

References

[1] BURGMAIER M, LIBERMAN A, MOLLMANN J, et al. Glucagon-like peptide-1(GLP-1)and its split products GLP-1(9-37)and GLP-1(28-37)stabilize atherosclerotic lesions in apoe/mice[J]. Atherosclerosis, 2013, 231: 427-435. DOI: 10.1016/j.atherosclerosis.2013.08.033.
[2] WEI Y, MOJSOV S. Distribution of GLP-1 and PACAP receptors in human tissues[J]. Acta Physiol Scand, 1996, 157: 355-357. DOI:10.1046/j.1365-201X.1996.42256000.x.
[3] 朱秋霄.利拉鲁肽对高糖条件下SD乳鼠心肌细胞P38MAPK信号通路作用的研究[D]. 石家庄:河北医科大学,2014:4-10.
[4] 杨胜利, 何作云, 冯兵, 等. 缺氧/复氧诱导培养人肥大心肌细胞凋亡模型的建立[J]. 重庆医学, 2004, 33(1):4-6. DOI: 10.3969/j.issn.1671-8348.2004.01.002.
[5] 谢琼慧, 赵超莉, 叶子青, 等.微小RNA-21对缺血缺氧大鼠心肌细胞凋亡的影响[J]. 中华烧伤杂志, 2014, 30(2):153-157.DOI: 10.3760/cma.j.issn.1009-2587.2014.02.014.
[6] NIKOLAIDIS L A, MANKAD S, SOKOS G G, et al. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion[J]. Circulation, 2004, 109(8):962-965. DOI: 10.1161/01.CIR.0000120505.91348.58.
[7] READ P A, KHAN F Z, DUTKA D P. Cardioprotection against ischemia induced by dobutamine stress using glucagon-like peptide-1 in patients with coronary artery disease[J]. Heart, 2012, 98(5): 408-413. DOI: 10.1136/hrt.2010.219345.
[8] NOYAN-ASHRAF M H, MOMEN M A, BAN K, et al. GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes af-ter experimental myocardial infarction in mice[J]. Diabetes, 2009, 58: 975-983. DOI: 10.2337/db08-1193.
[9] BATCHULUUN B, INOGUCHI T, SONODA, et al. Metformin and liraglutide ameliorate high glucose-induced oxidative stress via inhibition of PKC-NAD(P)H oxidase pathway in human aortic endothelial cells[J]. Atherosclerosis, 2014, 232: 156-164. DOI: 10.1016/j.atherosclerosis.2013.10.025.
[10] CHEN Y T, TSAI T H, YANG C C, et al. Exendin-4 and sitagliptin protect kidney from ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction[J]. J Transl Med, 2013, 11: 270. DOI: 10.1186/1479-5876-11-270.
[11] CHANG G, ZHANG D, YU H, et al. Cardioprotective effects of exenatide against oxidative stress-induced injury[J]. Int J Mol Med, 2013, 32: 1011-1020. DOI: 10.3892/ijmm.2013.1475.
[12] SHIRAKI A1, OYAMA J, KOMODA H, et al. The glucagon-like peptide 1 analog liraglutide reduces TNF-α-induced oxidative stress and inflammation in endothelial cells[J]. Atherosclerosis, 2012, 221(2): 375-382. DOI: 10.1016/j.atherosclerosis.2011.12.039.
[13] 陈旻, 明腾.心肌缺血再灌注损伤机制的研究进展[J]. 山东医药, 2014, 54(41): 98-100.DOI: 10.3969/j.issn.1002-266X.2014.41.040.
[14] 张丽娜,吴星恒. 心肌细胞凋亡与PI3K/Akt信号途径表达及其调控机制的研究[J].南昌大学学报(医学版),2010,50(5):119-121.
[15] 张金梁.游泳训练改善心梗造成的心肌氧化应激:激活PI3K-akt信号级联的核心作用[J]. 山东体育学院学报,2012, 28(5):62-67.DOI:10.3969/j.issn.1006-2076.2012.05.013.
[16] 郭敏,李世平,张彤哲,等.缬沙坦通过PI3K/Akt/eNOS通路保护2型糖尿病大鼠主动脉内皮细胞免受氧化损伤的研究[J].中国医药导报,2016,13(19):18-21.
[17] BOSE A K, MOCANU M M, CARR R D, et al. Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury[J]. Diabetes, 2005,54(1):146-151. DOI: 10.2337/diabetes.54.1.146.

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 14

Recommended Articles

Metrics

Comments

[1]	ZHU Jianping, LI Yunman. The key role of Nrf2 in ischemic stroke [J]. Journal of Hebei Medical College for Continuing Education, 2022, 39(2): 1-9.
[2]	. [J]. Journal of Hebei Medical College for Continuing Education, 2021, 38(5): 20-25.
[3]	. [J]. Journal of Hebei Medical College for Continuing Education, 2021, 38(2): 14-20.
[4]	. [J]. Journal of Hebei Medical College for Continuing Education, 2020, 37(5): 31-35.
[5]	. [J]. Medical Reserch and Education, 2019, 36(3): 1-7.
[6]	. [J]. Medical Reserch and Education, 2019, 36(1): 1-5.
[7]	. [J]. Medical Reserch and Education, 2018, 35(2): 26-31.
[8]	LI Dan, LUO Jingmei, ZHAO Lei, BING Yuyan, DU Luanying. Study on apoptosis of duodenum of mice infected with Trichinella spiralis [J]. Medical Reserch and Education, 2015, 32(6): 16-20.
[9]	QU Penghuan, SHI Jianhong. Advances on Y-box binding protein 1’s functions in the tumorigenesis and oncotherapy [J]. Medical Reserch and Education, 2015, 32(5): 74-77.
[10]	QU Penghuan, SHI Jianhong. Study on the mechanism of apoptosis and angiogenesis in promoting the development of fibrosis [J]. Medical Reserch and Education, 2015, 32(4): 33-37.
[11]	WANG Lin, NIU Pei, WU Bianying. Anti-injury effect of scutellarin on the hypoxic ischemic brain damage of neonatal rats and the expression of p38 MAPK [J]. Medical Reserch and Education, 2015, 32(2): 6-10.
[12]	LAI Yinxuan,HE Dongmei,YANG Limei,LIU Xinguang,LI Jiangbin. Effects of perna viridis polysaccharides on apoptosis of cervical cancer cell and expression of miRNA-34a [J]. Medical Reserch and Education, 2014, 31(2): 1-3.
[13]	MENG Ming,LIANG Hongge,FANG Hao,ZHOU Lei,FENG Jianyong,DONG Yang,YAN Zhen,CHEN Dongzhi. The significance of PI3K/Akt/mTOR pathway and autophagy in the proliferation of synovial cells in rheumatoid arthritis [J]. Medical Reserch and Education, 2013, 30(5): 69-74.
[14]	LI Chunhui,ZHENG Kebin,CUI Dongqiang,LI Zhihong,FANG Chuan. Effects of PTEN gene on the growth and apoptosis of glioma U251 cells [J]. Medical Reserch and Education, 2013, 30(5): 19-23.