【摘要】 目的 探讨利拉鲁肽(LIRA)对高糖诱导的H9c2细胞凋亡的影响。方法 在H9c2细胞的高糖培养液中加入LIRA、活性氧簇分子(ROS)清除剂N-乙酰半胱氨酸(NAC)、p38丝裂原活化蛋白激酶(p38MARK)抑制剂SB203580和c-Jurn氨基末端激酶(JNK)抑制剂SP600125等不同的处理因素作用24 h,采用流式细胞术检测细胞的凋亡,采用Western blot法检测H9c2细胞活化的含半胱氨酸的天冬氨酸蛋白水解酶3(c-caspase-3)、丝裂原活化蛋白激酶(MAPK)家族磷酸化的p38MAPK(p-p38MAPK)和JNK(p-JNK)的蛋白水平。结果 正常糖对照组、等渗透压对照组和高糖组(HG组)的细胞凋亡率分别为(1.04±0.11)%、(1.27±0.04)%和(28.60±1.08)%。与正常糖对照组比较,等渗透压对照组的细胞凋亡率差异无统计学意义(P>0.05),而HG组的细胞凋亡率显著增加(P<0.01)。HG+LIRA组、HG+NAC组、HG+SB203580组和HG+SP600125组的细胞凋亡率分别为(6.67±0.77)%、(3.65±0.26)%、(4.59±0.48)%和(4.22±0.89)%。与HG组比较,HG+LIRA组、HG+NAC组、HG+SB203580组和HG+SP600125组的凋亡率均明显下降(P<0.01)。与正常糖对照组比较,HG组心肌细胞内c-caspase-3、p-p38MAPK和p-JNK的蛋白表达水平明显上升(P<0.01)。与HC组比较,利拉鲁肽明显抑制了c-caspase-3蛋白水平(P<0.01),降低了p-p38MAPK和p-JNK的蛋白表达水平(P<0.05)。结论 利拉鲁肽可能通过抑制p38MAPK和JNK的磷酸化抑制高糖培养的H9c2细胞凋亡。更多还原

【Abstract】 Objective To investigate the effects of liraglutide on high glucose induced apoptosis of H9 c2 cardiomyocyte. Methods Different treatment factors were added into the H9 c2 cardiomyocyte culture solution for 24 h including liraglutide(LIRA), N-acetylcysteine(NAC) which is a reactive oxygenspecies(ROS) scavenger,SB203580 which is an inhibitor of p38 mitogen activated protein kinase(p38 MARK) and SP600125 which is an inhibitor of c-Jun N-terminal kinase(JNK). Cell apoptosis was detected by flow cytometrywhile, Western blotting was used to detect the activation of cysteinyl aspartate specific proteinase-3(c-caspase-3), the phosphorylation levels of p38 MAPK(p-p38 MAPK) and JNK(p-JNK). Results The apoptosis rates of normal glucosecontrol group( control group), equal osmotic pressure group and high glucose group( HG group) were(1.04±0.11)%,(1.27±0.04)% and(28.60 ± 1.08)% respectively. The apoptosis rates of HG + LIRA group,HG + NAC group,HG + SB203580 group and HG+SP600125 group were(6.67 ±0.77)%,(3.65 ±0.26)%,(4.59±0.48)% and(4.22±0.89)%respectively. Compared with the control group, there was no difference in the rate of apoptosis of equal osmotic pressure group(P>0.05),and the rate of apoptosis in HG group increased significantly(P<0.01).Compared with HG group, cell apoptosisin HG + LIRA group, HG + NAC group, HG + SB203580 group and HG + SP600 125 group decreased significantly(P <0. 01). Compared with the control group, the c-caspase-3,p-p38 MAPK and p-JNK protein levels increased significantly in the HG group( P < 0. 01).Compared with HG group, liraglutide significantly reduced the c-caspase-3, p-p38 MAPK and p-JNK protein expression levels. Conclusion Liraglutide may inhibit high glucose-induced apoptosis in H9 c2 cardiomyocyte through the inhibition of phosphorylation of p38 MAPK and JNK.更多还原