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目的探讨核转录因子NF-κB在单磷酰脂A预处理的延迟阶段的作用。方法建立大鼠心肌缺血/再灌注(I/R)损伤模型。分别应用单磷酰脂A(MLA)、NF-κB的特异性抑制剂DDTC加MLA预处理心脏,24h对心脏进行较长时间缺血再灌注,检测心肌梗死范围、LDH释放及心肌细胞凋亡率。另外分组检测MLA预处理0min、15min、30min、60min、NF-κB抑制剂DDTC加MLA预处理后30min时NF-κB活性。结果MLA预处理减小再灌注心肌梗死范围、降低血浆LDH活性、减少细胞凋亡(P<0.05vsI/R)。同MLA预处理组相比,DDTC+MLA组心肌梗死范围增大、LDH活性增高,细胞凋亡增加(P<0.05)。与预处理前相比,NF-κB活性在预处理后15min明显升高、30min达到高峰、60min下降(P<0.01)。与MLA预处理后15min、30min、60min相比,DDTC加MLA预处理后30min时,NF-κB活性明显降低(P<0.01),而与MLA预处理0min无显著差别(P>0.05)。结论(1)MLA预处理对24h后缺血/再灌注心肌有保护作用。(2)核转录因子NF-κB参与心肌预处理后的延迟保护作用,MLA预处理后NF-κB快速的核转移并激活可能是药物预处理延迟保护作用的重要机制之一。
Objective To investigate the role of NF-κB in the delayed phase of monophosphoryl lipid A pretreatment. Methods The rat model of myocardial ischemia / reperfusion (I / R) injury was established. Myocardial infarction, LDH release and cardiomyocyte apoptosis were detected by MLTC and MLTC pretreatment of MLA and MLA respectively. The heart was pretreated with MLA for 24 hours. rate. In addition, the activity of NF-κB in MLA pretreatment group at 0min, 15min, 30min and 60min, and NF-κB inhibitor DDTC plus MLA pretreatment at 30min were detected by subgroups. Results MLA preconditioning reduced the range of reperfusion myocardial infarction, decreased plasma LDH activity and decreased apoptosis (P <0.05vsI / R). Compared with the MLA preconditioning group, DDTC + MLA group increased myocardial infarct size, increased LDH activity and increased apoptosis (P <0.05). Compared with that before pretreatment, NF-κB activity increased significantly 15 min after preconditioning, reached the peak at 30 min and decreased at 60 min (P <0.01). Compared with MLA preconditioning for 15min, 30min and 60min, the activity of NF-κB decreased significantly (P <0.01) at 30 min after pretreatment with MLTC plus MLA, but no significant difference with MLA pretreatment at 0 min (P> 0.05). Conclusions (1) MLA pretreatment has a protective effect on myocardial ischemia / reperfusion after 24h. (2) The nuclear factor NF-κB is involved in the delayed protection after myocardial preconditioning. The fast nuclear translocation and activation of NF-κB may be one of the important mechanisms of delayed preconditioning.