α-硫辛酸对肾缺血再灌注损伤大鼠心肌细胞凋亡的影响

Effect of alpha-lipoic acid on cardiomyocyte apoptosis following renal ischemia-reperfusion injury in rats

目的评价α-硫辛酸对肾缺血再灌注损伤大鼠心肌细胞凋亡的影响。方法健康雄性SD大鼠36只，体重250～280g，采用随机数字表法，将其随机分为3组：假手术组（S组）、肾缺血再灌注组（I／R组）和α-硫辛酸组（L组），每组12只。I／R组和L组采用夹闭双侧肾动、静脉45min后恢复灌注的方法制备大鼠肾缺血再灌注损伤模型，S组不夹闭双侧肾蒂。L组于夹闭前20min和再灌注前20min分别尾静脉注射α-硫辛酸30mg／kg，I／R组分别尾静脉注射等容量溶剂（35％聚乙二醇＋60％生理盐水＋5％乙醇）。于再灌注24h抽取腹主动脉血，测定血清肌酐（Cr）和MDA浓度，随后处死大鼠取心脏，测定心肌MDA含量和SOD活性，采用流式细胞术检测心肌细胞凋亡率，采用免疫组化法测定心肌细胞Bcl-2及Bax的表达，计算Bcl-2／Bax比值。结果与S组相比，I／R组和L组血清Cr和MDA浓度、心肌MDA含量和心肌细胞凋亡率升高，SOD活性降低，I／R组Bcl-2／Bax比值降低（P〈0．05）；与I／R组相比，L组血清Cr和MDA浓度、心肌MDA含量和心肌细胞凋亡率降低，SOD活性升高，Bcl-2／Bax比值升高（P〈0．05）。结论α-硫辛酸可减轻肾缺血再灌注损伤大鼠心肌损伤，与抑制心肌细胞凋亡有关。

Objective To evaluate the effect of alpha-lipoic acid （ALA） on cardiomyocyte apoptosis fol/owing renal isehemia-reperfusion injury（RIRI） in rats. Methods Thirty-six male SD rats weighing 250-280 g were randomly divided into 3 groups （n = 12 each）： group sham operation （group S）; group I/R and group I/R ＋ ALA （ group L）. The model of RIRI was produced by occlusion of renal artery and vein for 45 min followed by 24 h reperfusion, in group S the renal pedicles were exposed but not occluded. In group L ALA infusion （30 mg/kg） was given via tail vein at 20 min before ischemia and at 20 rain before reperfusion, while in group I/R the equal volume of solution （35 % polyethylene glycol ＋ 60% physiological saline ＋ 5% ethanol） was infused instead of ALA. The animals were sacrificed at the end of 24 h of reperfusion, blood samples were taken for detecting concen- trations of serum creatinine （Cr） and malondialdehyde （MDA）. Then the hearts were immediately removed for determination of SOD activity, MDA content, cardiomyocyte apoptosis （flow cytometry） and Bcl-2/Bax ratio （immuno- histology）. Results Serum Cr concentration, serum and myocardium MDA levels and cardiomyocyte apoptosis were significantly increased after RIRI in groups I/R and L as compared with group S （ P 〈 0.05） . ALA treatment significantly decreased serum Cr concentration, serum and myocardium MDA levels, cardiomyoeyte apoptosis and increased SOD activity and Bcl-2/Bax ratio （ P 〈 0.05）. Conclusion ALA can attenuate myocardium injury by inhibiting cardiomyocyte apoptosis following RIRI in rats.