丙泊酚减轻缺氧/复氧诱导的心肌细胞损伤

Propofol reduces anoxia-reoxygenation-induced injury of cardiomyocytes

目的探讨丙泊酚(Pro)通过调控JNK/p38 MAPK通路对缺氧/复氧诱导的心肌细胞损伤的影响。方法将细胞分为对照(control)组、缺氧/复氧(A/R)组、缺氧/复氧+Pro低、中、高剂量(A/R+Pro-L、A/R+Pro-M、A/R+Pro-H)组、缺氧/复氧+Pro+p38 MAPK通路抑制剂(A/R+Pro+SB203580)组。用流式细胞测量术检测细胞的凋亡;Western blot检测Bcl-2、Bax、cleaved caspase-3和JNK/p38 MAPK信号通路相关蛋白的表达;ELISA检测乳酸脱氢酶(LDH)含量、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性和过氧化氢酶(CAT)活性。结果A/R组明显抑制细胞Bcl-2蛋白表达和OD、CAT活性,而促进细胞凋亡和Bax蛋白、cleaved caspase-3蛋白、LDH、MDA、p-JNK蛋白、p-p38 MAPK蛋白的表达(P<0.05)。与A/R组相比,A/R+Pro-L组、A/R+Pro-M组、A/R+Pro-H组明显促进细胞的Bcl-2蛋白表达和SOD、CAT活性,而抑制细胞凋亡和Bax蛋白、cleaved caspase-3蛋白、LDH、MDA、p-JNK蛋白、p-p38 MAPK蛋白的表达(P<0.05)。与A/R+Pro组相比,A/R+Pro+SB203580组明显促进细胞的Bcl-2蛋白表达和SOD、CAT活性,而抑制细胞凋亡、p-JNK蛋白、p-p38 MAPK蛋白、Bax蛋白、cleaved caspase-3蛋白表达和LDH、MDA活性(P<0.05)。结论Pro可能通过调控JNK/p38 MAPK通路减缓缺氧/复氧诱导的心肌细胞凋亡和氧化应激。

Objective To investigate the effect of propofol(Pro)on cardiomyocyte damage induced by anoxia-reoxygenation through regulating JNK/p38 MAPK pathway.Methods Divided the cells into control group,anoxia-reoxygenation(A/R)group,anoxia-reoxygenation+propofol of low,medium and high dose(A/R+Pro-L,A/R+Pro-M,A/R+Pro-H)group,anoxia-reoxygenation+propofol+p38 MAPK pathway inhibitor(A/R+Pro+SB203580)group.Flow cytometry was used to detect cell apoptosis;Western blot was used to detect the expression of Bcl-2,Bax,cleaved caspase-3 and JNK/p38 MAPK signaling pathway related proteins;ELISA was applied to detect LDH content,MDA content,SOD activity and CAT activity.Results In A/R group Bcl-2 protein expression SOD and CAT activity were significantly inhibited cell apoptosis rate,Bax protein,cleaved caspase-3 protein expression,LDH,MDA,p-JNK protein,p-p38 MAPK protein expression were promoted(P<0.05).Compared with A/R group,A/R+Pro-L group,A/R+Pro-M group,A/R+Pro-H group all showed significantly promoted cell Bcl-2 protein expression,SOD,CAT activity;inhibition of cell apoptosis,Bax protein,cleavedcaspase-3 protein,LDH,MDA,p-JNK protein and p-p38 MAPK protein(P<0.05).Compared with the A/R+Pro group,the A/R+Pro+SB203580 group showed significantly promoted cell Bcl-2 protein expression,SOD,CAT activity and inhibited cell apoptosis,p-JNK protein,p-p38 MAPK protein,Bax protein,cleaved caspase-3 protein,LDH and MDA(P<0.05).Conclusions Propofol may slow down anoxia-reoxygenation induced cardiomyocyte apoptosis and oxidative stress through regulating the JNK/p38 MAPK pathway.