胰高血糖素样肽1对乳鼠心肌细胞凋亡的影响及其机制

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16 h、复氧4 h,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+U0126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[(36 809±4750)RLU比(57 602±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(PI3K抑制剂)和UO126(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PI3K/Akt和MAPK所介导的抗细胞凋亡作用有关.

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

Objective To observe the effect of glucagon-like peptide-1 (GLP-1) on hypoxia-reoxygenation (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 + UO126 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, Caspsse-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 Caspsse-3 activity (36 809±4750) RLU vs. (57 602±9161) RLU, P < 0.01], while LY294002 (PBK 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.