不同剂量的地塞米松对大鼠缺血再灌注心肌细胞凋亡及核因子кB表达的影响

Effect of different dexamethasone doses on apoptosis of myocardiocytes and expression of NF-кB in rats following ischemia/reperfusion

目的探讨不同剂量地塞米松预处理对大鼠缺血再灌注(I/R)心肌细胞凋亡及NF-κB表达的影响。方法 64只SD大鼠,随机分为大剂量组、中剂量组、小剂量组及对照组,每组1 6只,分别予2.5、0.8和0.4 mg/kg的地塞米松及蒸馏水预处理。预处理24 h后,构建体外心脏I/R模型,观测缺血前期及再灌注期左心室发展压(LVDP)、左心室压力最大上升和下降速率(±dp/dt_(max))、冠状动脉流出量(CF);测冠状动脉流出液肌酸磷酸激酶同工酶(CK MB)漏出率;TUNEL法检测心肌细胞凋亡;免疫组织化学法检测NF-κB活化水平。结果与对照组比较,大、中剂量组LVDP、±dp/dt_(max)及CF明显改善(P<0.05),CK-MB漏出率明显降低(P<0.05),心肌细胞凋亡指数及NF-κB表达明显减少(P<0.01);小剂量组上述指标虽有改善,但差异无统计学意义(P>0.05)。结论地塞米松预处理对大鼠I/R的心肌保护作用可能与抑制NF-κB活性,减少心肌细胞凋亡有关,且有一定的剂量依赖性。

Objective To study the effect of pretreatment with different dexamethasone doses on apoptosis of myocardiocytes and expression of NF-κB in rats following ischemia/reperfusion（I/R）.Methods Sixty-four SD rats were randomly divided intogroup A,group B,group C and control group（16 in each group）.24 h after the animals were pretreaded with dexamethasone at 2.5,0.8,0.4 mg/kg and distilled water respectively,an I/R model was established.Left ventricular developed pressure（LVDP）,maximal left ventricular pressure increase and minimal left ventricular pressure decrease（±dp/dtmax）,and coronary artery flow（CF） in the rats were dynamically minitored.CK-MB level in coronary artery flow was measured.Apoptosis of myocardiocytes was assayed by TUNEL and NF-κB activation was detected by immunohistochemistry.Results The LVDP,±dp/dtmax and CF were significantly higher while the leakage of CK-MB,apoptosis of myocardiocytes and expression level of NF-κB were significantly lower in groups A and B than in control group during I/R（P〈0.05）.No significant difference was observed in LVDP,±dp/dtmax,CF,leakage of CK-MB,apoptosis of myocardiocytes and expression level of NF-κB in group C although they were more or less improved.Conclusion Pretreatment with dexamethasone can protect rat myocardium during I/R in a dose-dependent manner by inhibiting NF-κB activation and reducing apoptosis of myocardiocytes.