The anti-apoptotic pro-survival kinase signaling cascades,phosphatidylinositol-3-OH kinase(PI3K)-Akt and p42/p44 extra-cellular signal-regulated protein kinases(ERK 1/2),which have been termed the reperfusion injury salvage kinase(RISK)pathway,are involved in cellular survival.In myocardial ischemic preconditioning,pharmacological preconditioning,ischemic postconditioning and pharmacological postconditioning,the activation of these kinase cascades at the time of reperfusion has been demonstrated to confer cardioprotection against reperfusion-induced injury.Targeting the RISK signaling pathway may provide a novel strategy to salvaging viable myocardium and limiting infarct size during myocardial ischemia-reperfusion.
目的:研究吡咯-咪唑聚酰胺(PIP)对凝集素样氧化型低密度脂蛋白受体-1(LOX-1)受体启动子基因的调控,并探讨其对抗大鼠肾脏损害的作用。方法:雄性SD大鼠50只,按随机数字法将大鼠分为五组,每组10只。A组:普通饲料,未用PIP。B组:高脂饲料(含3%胆固醇+10%猪油),未用PIP。C组:高脂饲料,PIP干预组,C1组按10μg/(kg·d)静脉注射;C2组按5μg/(kg·d)静脉注射。D组:高脂饲料,他汀干预组,瑞舒伐他汀5 mg/(kg·d)灌胃给药。治疗时间均为8周。检测肾组织LOX-1 m RNA、MMP-9 m RNA表达水平,测定血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)含量,测定24 h尿蛋白定量、血尿素氮(BUN)和肌酐(Scr)水平。结果:C1组、C2组大鼠肾组织LOX-1 m RNA、MMP-9 m RNA表达水平均较B组低,差异均有统计学意义(P<0.01);C1组、C2组大鼠血清TC、TG、HDL-C、LDL-C水平与B组比较差异均无统计学意义(P>0.05);C1组、C2组大鼠24 h尿蛋白定量较B组明显降低(P<0.01),而血BUN、Scr水平与A组比较差异均无统计学意义(P>0.05)。结论:PIP化合物能明显下调高脂血症大鼠肾组织LOX-1 m RNA表达,改善肾功能及抑制肾脏损害。
