苦碟子预先给药对运动力竭致大鼠心肌损伤时HIF-1α表达的影响

Effect of ixeris sonchifolia pretreatment on expression of hypoxia-inducible factor-1αfollowing myocardial injury induced by exhausting exercise in rats

目的评价苦碟子预先给药对运动力竭致大鼠心肌损伤时缺氧诱导因子-1α(HIF-1α)表达的影响。方法清洁级健康雄性Wistar大鼠56只,2月龄,体重200~220 g,采用随机数字表法分为3组:对照组(C组,n=8)、运动力竭组(E组,n=24)和苦碟子预先给药组(IS组,n=24)。E组和IS组采用游泳法制备运动力竭致大鼠心肌损伤模型,IS组于腹腔注射苦碟子20 ml/kg后行力竭运动。E组和IS组于游泳致力竭后即刻、6和24 h(T1-3)时采集下腔静脉血样,采用ELISA法检测血清心肌肌钙蛋白I(cTnI)浓度;麻醉后处死大鼠取心肌组织,采用TUNEL法确定心肌细胞凋亡指数;采用免疫组化法检测心肌HIF-1α、Bax及Bcl-2的表达,计算Bcl-2/Bax比值;采用HBFP法观察大鼠心肌损伤面积。结果与C组比较,E组和IS组各时点心肌损伤面积增加,血清cTnI浓度、心肌细胞凋亡指数和Bcl-2/Bax比值升高,HIF-1α表达上调(P<0.05);与E组比较,IS组各时点心肌损伤面积减少,血清cTnI浓度、心肌细胞凋亡指数和Bcl-2/Bax比值降低,HIF-1α表达下调(P<0.05)。结论苦碟子预先给药减轻运动力竭致大鼠心肌损伤的机制与其抑制HIF-1α表达上调,减少心肌细胞凋亡有关。

Objective To evaluate the effect of ixeris sonchifolia pretreatment on the expression of hypoxia-inducible factor-1α(HIF-1α)following myocardial injury induced by exhausting exercise in rats.Methods Fifty-six healthy clean-grade male Wistar rats,weighing 200-220 g,were divided into 3 groups using a random number table method:control group(group C,n=8),exhausting exercise group(group E,n=24)and ixeris sonchifolia pretreatment group(group IS,n=24).In E and IS groups,the model of myocardial injury was established by exhausting swimming.In group IS,the rats were subjected to exhausting swimming after intraperitoneal ixeris sonehifolia 20 ml/kg.In E and IS groups,blood samples were taken from the inferior vena cava at 0,6 and 24 h after exhaustion(T1-3)for determination of serum cardiac troponin I(cTnI)concentrations by enzyme-linked immunosorbent assay.The animals were sacrificed after anesthesia,and myocardial specimens were obtained for determination of the cell apoptosis index(by TUNEL)and expression of HIF-1α,Bax and Bcl-2(by immunohistochemistry),and Bax/Bcl-2 ratio was calculated.The area of myocardial injury was observed using HBFP assay.Results Compared with group C,the area of myocardial injury,concentration of serum cTnl,Bax/Bcl-2 ratio and apoptosis index were significantly increased,and the expression of HIF-1αin myocardial tissues was up-regulated at each time point in E and IS groups(P<0.05).Compared with group E,the area of myocardial injury,concentration of serum cTnl,Bax/Bcl-2 ratio and apoptosis index were significantly decreased,and the expression of HIF-1αin myocardial tissues was down-regulated at each time point in group IS(P<0.05).Conclusion The mechanism by which ixeris sonchifolia pretreatment mitigates myocardial injury induced by exhausting exercise is related to inhibiting up-regulated expression of HIF-1αin myocardial tissues and reducing cell apoptosis in rats.