胰高血糖素样肽1对乳鼠心肌细胞凋亡的影响及其机制  

Effect of glucagon-like deptide-1 on hypoxia-reoxygenation induced injury in neonatal rat cardiomyocytes

作　　者：王绍欣[1] 谢云[1] 周雪[2] 沙伟伟[3] 汪玮琳[1] 韩丽萍[1] 王家驰[1] 于德民[1] 

机构地区：[1]天津医科大学代谢病医院糖尿病神经内科卫生部激素与发育重点实验室,300070 [2]河北省保定市解放军第二五二医院内分泌科 [3]北京市昌平区医院ICU室

出　　处：《中华心血管病杂志》2010年第1期72-75,共4页Chinese Journal of Cardiology

摘　　要：目的研究胰高血糖素样肽1（GLP-1）对缺氧复氧诱导的乳鼠心肌细胞损伤的影响及其可能机制。方法通过给原代培养的乳鼠心室肌细胞缺氧16h、复氧4h，建立缺氧复氧（H／R）心室肌细胞损伤模型。于缺氧前随机分为正常对照组，H／R组，GLP-1＋H／R组，GLP-1＋H／R＋UO126组，GLP-1＋H／R＋LY294002组，H／R＋U0126组和H／R＋LY294002组。H／R损伤后测定上清液中乳酸脱氢酶（LDH）活性、细胞凋亡率和半胱天冬酶-3（Caspase-3）活性。结果H／R组LDH活性、细胞凋亡率和Caspase-3活性均明显高于正常对照组（P均〈0．01）。而GLP-1＋H／R组LDH活性[（128．47±7．96）U／L比（223．96±22．10）U／L，P〈0．01]、细胞凋亡率[（2．84±2．56）％比（12．58±6．69）％，P〈0．01]和Caspase-3活性[（36809±4750）RLU比（57602±9161）RLU，P〈0．01]则明显低于H／R组，但上述指标变化可分别被LY294002（P13K抑制剂）和U0126（MAPK抑制剂）抑制。结论GLP-1可以直接作用于心肌细胞，对H／R诱导的心肌细胞损伤产生一定的保护作用，保护作用可能主要是通过抑制心肌细胞的凋亡实现的，并且GLP-1对凋亡的抑制作用可能与PBK／Akt和MAPK所介导的抗细胞凋亡作用有关。Objective To observe the effect of glucagon-like peptide-1 （GLP-1） on hypoxiareoxygenation （H/R） induced injury in neonatal rat cardiomyocytes. Methods Cultured neonatal rat cardiomyocytes were randomly divided into seven groups： normal control group, H/R group, GLP-1 ± H/R group, GLP-1 ± H/R ± U0126 group, GLP-1 ± H/R ± LY294002 group, H/R ± U0126 group, H/R ± LY294002 group. LDH activity, apoptosis rate of cardiomyocytes, Caspase-3 activity were detected. Results Compared with normal control group, the activity of LDH, cardiomyocyte apoptosis rate, Caspase-3 activity were all significantly increased in H/R group （ all P 〈 0.01 ）. However, compared with H/R group, these changes were significantly attenuated in GLP-1 ± H/R group [ the activity of LDH （ 128.47 ±7.96） U/L vs. （223.96 ± 22. 10） U/L, P 〈 0. 01, and cardiomyocyte apoptosis rate （2.84 ± 2.56 ） % vs. （ 12.58 ± 6.69） %, P 〈0.01, and Caspase-3 activity （36 809 ±4750） RLU vs. （57 602 ±9161） RLU, P 〈0.01 ], while LY294002 （PI3K inhibitor） and U0126 （MAPK inhibitor） could block the effects of GLP-1 in cardiomyocytes underwent H/R injury. Conclusions GLP-1 could protect H/R injury mainly by inhibiting cardiomyocytes apoptosis via activating PI3K/Akt and MAPK signaling pathway.

关 键 词：肌细胞 心脏 胰高血糖素样肽1 细胞凋亡 缺氧复氧 

分 类 号：R341[医药卫生—基础医学]