缺血预处理对大鼠冷保存供肝细胞HMG-CoA还原酶活力的影响

目的 观察缺血预处理对大鼠冷保存供肝细胞HMG-CoA还原酶(HMGCR)活力的影响,探讨缺血预处理减轻大鼠供肝冷保存损伤的机制.方法 将25只大鼠随机分为对照组(C组)、冷保存组(Ⅰ组)、缺血预处理组(IP组)、阿托伐他汀30 μmol/L和100μmol/L处理组(A30组和A100组),每组5只.C组为正常大鼠肝脏,4℃UW液灌注;Ⅰ组为灌注后冷保存8 h;IP组先给予缺血预处理,灌注后冷保存8 h;A30组和A100组先给予缺血预处理,用终质量浓度为30μmol/L和100μmol/L的阿托伐他汀UW液灌注后再置入含30μmol/L和100μmol/L的阿托伐他汀UW液中4℃冷保存8 h.分别测定5组大鼠肝脏的HMGCR活力.结果 供肝经过8 h冷保存后(Ⅰ)HMGCR活性为(1872±157)nmol/(min·mg),与对照组(C)(3298±224)nmol/(min·mg)比较明显下降(P＜0.05),给予缺血预处理后再给予冷保存(IP),则HMGCR活性为(3746±231)nmol/(min·mg),明显升高(P＜0.05);给予缺血预处理同时给予HMGCR抑制剂阿托伐他汀则HMGCR活性则受到明显抑制,并随着阿托伐他汀浓度的增加而抑制效应更为明显,A30组、A100组HMGCR酶活力分别为(2010±193)nmol/(min·mg)、(1469±132)nmol/(min·mg),同IP组比较明显下降(P＜0.05).结论 缺血预处理可以明显提高HMGCR活力,而阿托伐他汀则可消除缺血预处理升高HMGCR活性的作用;缺血预处理升高HMGCR活力的机制是增加HMGCR蛋白的表达.

Abstract：

Objective To investigate the effects of ischemic preconditioning on the activity of 3-hydroxy-3-methylglutary coenzyme A reductase (HMGCR) of hepatocytes following cryopreservation in rats. Methods Twenty-five rats were randomly divided into five groups: control group ( C), cryopreservation group (Ⅰ), ischemic preconditioning group (IP), atorvastatin (30 γμmol/L) treatment group (A30) and atorvastatin (100 μmol/L) treatment group (A100). In control group, normal donor livers were flushed with 4 ℃ UW solution. In group I, donor livers were cryopreserved for 8 h after UWs flushing. In group IP, donor livers were subjected to ischemic preconditioning, and then flushed and cryopreserved in UWs. In group A30, donor livers were treated as in group I except that 30 μmol/L atorvastatin was added to the UWs. In group A100, donor lovers were treated as in group I with the exception that 100 μmol/L atorvastatin was added to the UWs. The activity of HMGCR was assessed. Results HMGCR activity in the donor cantly increased after ischemic preconditioning[(3746±231 ) nmol/(min-mg)]. The enhanced HMGCR activity induced by ischemic preconditioning was inhibited by atorvastatin in a concentration-dependent mantivity by up-regulating its protein expression and this effect can be abrogated by atorvastatin.

Effects of ischemic preconditioning on the activity of HMGCR of hepatocytes following cryopreservation in rats

Objective To investigate the effects of ischemic preconditioning on the activity of 3-hydroxy-3-methylglutary coenzyme A reductase (HMGCR) of hepatocytes following cryopreservation in rats. Methods Twenty-five rats were randomly divided into five groups: control group ( C), cryopreservation group (Ⅰ), ischemic preconditioning group (IP), atorvastatin (30 γμmol/L) treatment group (A30) and atorvastatin (100 μmol/L) treatment group (A100). In control group, normal donor livers were flushed with 4 ℃ UW solution. In group I, donor livers were cryopreserved for 8 h after UWs flushing. In group IP, donor livers were subjected to ischemic preconditioning, and then flushed and cryopreserved in UWs. In group A30, donor livers were treated as in group I except that 30 μmol/L atorvastatin was added to the UWs. In group A100, donor lovers were treated as in group I with the exception that 100 μmol/L atorvastatin was added to the UWs. The activity of HMGCR was assessed. Results HMGCR activity in the donor cantly increased after ischemic preconditioning[(3746±231 ) nmol/(min-mg)]. The enhanced HMGCR activity induced by ischemic preconditioning was inhibited by atorvastatin in a concentration-dependent mantivity by up-regulating its protein expression and this effect can be abrogated by atorvastatin.