利拉鲁肽对缺氧/复氧条件下乳鼠心肌细胞PI3K途径信号通路的作用

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

医学研究与教育 ›› 2018, Vol. 35 ›› Issue (6): 24-29.DOI: 10.3969/j.issn.1674-490X.2018.06.005

利拉鲁肽对缺氧/复氧条件下乳鼠心肌细胞PI3K途径信号通路的作用

周雪¹,李贲²,李志红¹,郭淑芹¹,张文娟¹

1.保定市第一中心医院内分泌科, 河北保定 071000;
2.河北大学附属医院胸外科, 河北保定 071000

收稿日期:2017-08-01 出版日期:2018-12-25 发布日期:2018-12-25
通讯作者: 李志红(1972—),女,河北保定人,主任医师,博士,主要从事糖尿病及其并发症、甲状腺及骨代谢疾病的研究。E-mail: lizhihonglfz@126.com
作者简介:周雪(1980—),女,回族,河北黄骅人,副主任医师,硕士,主要从事糖尿病及其并发症、甲状腺及骨代谢疾病的研究。 E-mail: m15831219249@163.com
基金资助:
保定市科学技术研究与发展计划项目(16ZF110)

Received:2017-08-01 Online:2018-12-25 Published:2018-12-25

摘要/Abstract

摘要： 目的探讨利拉鲁肽对缺氧/复氧(H/R)诱导的心肌细胞损伤是否具有保护作用及其可能机制。方法成功培养乳鼠心肌细胞作为实验对象,分为5组:正常对照组(A组),单纯H/R组(B组),利拉鲁肽+ H/R组(C组),H/R+利拉鲁肽+LY294002组(D组), H/R+ LY294002组(E组),n=8,对5组分别检测细胞上清液乳酸脱氢酶(LDH)、丙二醛(MDA)水平以及超氧化物歧化酶(SOD)活性,以流式细胞仪双染法检测各组心肌细胞凋亡率以及凋亡酶半胱氨酸天冬氨酸特异性蛋白酶-3(Caspase-3)活性。结果与A组比较,B组LDH、MDA、细胞凋亡率、Caspase-3活性明显增高(P<0.01),SOD活性则降低(P<0.01);而与B组比较,C组LDH、MDA、细胞凋亡率、Caspase-3活性则降低(P<0.01),SOD活性升高(P<0.01);与C组比较,给予磷脂酰肌醇3激酶(PI3K)抑制剂LY294002的D组LDH、MDA、细胞凋亡率、Caspase-3活性有所增加(P<0.01), SOD活性降低(P<0.01);E组上述指标的变化与B组相比没有统计学意义(P>0.05)。结论 H/R对心肌细胞造成了损伤,而利拉鲁肽直接作用于心肌细胞,可能通过抗氧化应激损伤、抑制细胞凋亡等机制对心肌细胞产生一定程度的保护作用,而PI3K途径可能与利拉鲁肽的抗凋亡及抗氧化应激作用机制有关。

关键词: 利拉鲁肽, 缺氧/复氧, 心肌细胞, 凋亡, 氧化应激, 磷脂酰肌醇3激酶

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

中图分类号:

周雪,李贲,李志红,郭淑芹,张文娟. 利拉鲁肽对缺氧/复氧条件下乳鼠心肌细胞PI3K途径信号通路的作用[J]. 医学研究与教育, 2018, 35(6): 24-29.

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利拉鲁肽对缺氧/复氧条件下乳鼠心肌细胞PI3K途径信号通路的作用

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