比索洛尔通过 ASK1-JNK/ p38 MAPK 信号通路改善 缺血再灌注诱导的 H9C2 心肌细胞损伤的研究.

OBJECTIVE: To probe into the effect of bisoprolol on H9C2 cardiomyocyte injury induced by ischemia reperfusion (I/ R) and its mechanism. METHODS: H9C2 cardiomyocytes were cultured in vitro and divided into the control group ( Control group ), hypoxia / reoxygenation ( H / R) model group ( Model group ), bisoprolol group (Bisoprolol group), bisoprolol + apoptosis signal-regulated kinase 1 (ASK1) recombinant protein group (Bisoprolol+ ASK1 group). Except for the Control group, the H9C2 cardiomyocytes were treated with H / R injury in the rest groups. The cell viability was detected by cell counting kit (CCK8) method; the cell apoptosis was detected by flow cytometry; the myocardial injury markers [ lactate dehydrogenase ( LDH ), cardiac troponin T ( cTnT )] and inflammatory factors [ interleukin 6 ( IL-6), interleukin 1β ( IL-1β) and tumor necrosis factor α (TNF-α)] levels were measured by enzyme-linked immunosorbent assay; the calcium ion concentration in cells was measured by laser confocal assay; the ASK1-c-Jun amino-terminal kinase ( JNK) / p38 mitogen-activated protein kinase ( p38 MAPK) signaling pathway-related protein expression was detected by Western blotting. RESULTS: Compared with the Control group, the H9C2 cell viability, LDH and cTnT levels were lower, the cell apoptosis rate, IL-6, IL-1β and TNF-α levels were higher, the calcium ion concentration, p-ASK1 / ASK1, p-JNK/ JNK and p-p38 MAPK/ p38 MAPK ratio were higher in the Model group, with statistically significant differences (P<0. 05). Compared with the Model group, the H9C2 cell viability, LDH and cTnT levels were higher, the cell apoptosis rate, IL-6, IL-1β and TNF-α levels were lower, the calcium ion concentration, p-ASK1 / ASK1, p-JNK/ JNK and p-p38 MAPK/ p38 MAPK ratio were lower in the Bisoprolol group and Bisoprolol + ASK1 group, with statistically significant differences ( P < 0. 05). Compared with the Bisoprolol group, the H9C2 cell viability, LDH and cTnT levels were lower, the cell apoptosis rate, IL-6, IL-1β and TNF-α levels were higher, the calcium ion concentration, p-ASK1 / ASK1, p-JNK/ JNK and p-p38 MAPK/ p38 MAPK ratio were higher in the Bisoprolol +ASK1 group, with statistically significant differences (P<0. 05). CONCLUSIONS: Bisoprolol can improve H9C2 cardiomyocyte injury induced by I/ R through inhibiting inflammatory response and calcium overload, its mechanism may related to the inhibition of ASK1-JNK/ p38 MAPK signaling pathway activation. [ABSTRACT FROM AUTHOR]