匹立尼酸对大鼠肝脏冷保存损伤的保护作用

Protective effect of pirinixic acid against cold preservation injury to rat liver

目的:观察匹立尼酸(pirinixic acid)对大鼠肝脏冷保存损伤的保护作用。方法:将60只SD大鼠随机均分为匹立尼酸预处理组和对照组,匹立尼酸预处理组分别于术前2 d,1 d和1 h尾静脉注射匹立尼酸[3 mg(/kg.d)],对照组相应给予等体积的溶剂。切取两组大鼠肝脏,放入4℃林格氏液中保存。两组分别于保存0(保存前),2,4,6,8 h时间点各取6例肝脏标本,用RT-PCR,Western blot法检测肝组织过氧化物酶体增殖物激活剂受体α(PPARα)mRNA及蛋白表达量,免疫组织化学法检测肝细胞内核因子κB(NF-κB)活性,并行肝组织病理学检查。结果:随着冷保存时间的延长,两组肝组织中PPARαmRNA和表达蛋白的量均逐渐降低,肝组织病理学评分逐渐增高,但同一时间点匹立尼酸预处理组PPARαmRNA和表达蛋白的量高于对照组,病理组织学评分低于对照组,差异均有统计学意义(均P<0.05);除对照组在8 h时间点外,两组肝细胞内NF-κB的活化水平随着冷保存时间的延长均逐渐增高,且同一时间点匹立尼酸预处理组NF-κB活化水平低于对照组(均P<0.05)。结论:匹立尼酸对大鼠肝脏冷保存损伤具有保护作用,其机制可能与其上调PPARα的表达、抑制NF-κB的活化有关。

Objective： To observe the protective effect of pirinixic acid on cold storage injury to rat liver. Methods： Sixty SD rats were equally randomized into pirinixic acid pretreatment group and control group.Rats in pirinixic acid pretreatment group were given pirinixic acid [3 mg/（kg·d）] at 2 d,1 d and 1 h before surgery by tail vein injection,and rats in control group were given vehicle at the same volume instead.The livers were then removed from rats of the two groups and preserved in 4 oC℃ Ringer＇s solution.Liver specimens of the two groups were studied after cold preservation for 0（before cold preservation）,2,4,6 and 8 h respectively,and 6 specimens were obtained in each group at each time point.The mRNA and protein expression levels of peroxisome proliferator-activated receptors α（PPARα） were detected by RT-PCR and Western blot,respectively.The activities of nuclear factor-κB（NF-κB） in hepatic cells were measured by using immunohistochemical staining,and pathological examinations were also performed. Results： With prolongation of the preservation time,the expression levels of mRNA and protein of PPARα in the liver tissues were decreased,and the pathological scores of liver increased gradually in both groups,but in the same time points,the expression levels of mRNA and protein of PPARα in pirinixic acid pretreatment group were higher than those in control group,and the pathological score of pirinixic acid pretreatment group was lower than that of control group,and all the differences had statistical significances（all P0.05）.Except for the control group at 8 h time point,the activities of NF-κB in hepatocytes of the both groups were increased gradually with the extension of the preservation time,and NF-κB activity of pirinixic acid pretreatment group was significantly lower than that of control group at the same time points（all P0.05）. Conclusion： Pirinixic acid has protective effect against cold preservation injury of liver in rats,and its mechanism is probably associated with up-regulating PPARα expression and inhibiting NF-κB activation.