α-硫辛酸对肾缺血再灌注损伤大鼠心肌细胞凋亡的影响

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250～280 g,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45 min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20 min和再灌注前20 min分别尾静脉注射α-硫辛酸30 mg/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JR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.

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

Objective To evaluate the effect of alpha-lipoic acid (ALA) on cardiomyocyte apoptosis following renal ischemia-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 mln before ischemia and at 20 min 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 saerificed at the end of 24 h of reperfusion,blood samples were taken for detecting concentrations 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 (immunohistology).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,cardiomyocyte 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.