摘要
目的 观察异甘草酸镁联合维拉帕米对肝切除肝缺血再灌注损伤的保护作用.方法 将雄性SD大鼠数字随机法分为假手术组（A组）、50％肝切除肝缺血再灌注损伤组（B组）、50％肝切除肝缺血再灌注损伤＋异甘草酸镁治疗组（C组）、50％肝切除肝缺血再灌注损伤＋维拉帕米治疗组（D组）、50％肝切除肝缺血再灌注损伤＋异甘草酸镁联合维拉帕米治疗组（E组）.观察各组大鼠肝脏丙氨酸转氨酶（A LT）、形态学、超氧化物歧化酶（SOD）活性[以每克肝组织中硝酸盐单位（NU/g）表示]、凋亡相关基因（FasL）、半胱氨酸蛋白酶3（Caspase-3）及β-连环蛋白（[3-catenin）的表达情况.结果 与B组比较,E组各时间点血清ALT水平[6、12、24、48 h分别为（354.2 ±63.4）、（452.2±79.6）、（1 243.2±124.9）、（423.3 ±64.3）U/L]与B组比较[6、12、24、48 h分别为（887.2 ±118.6）、（1 234.5±155.7）、（2 124.8 ±234.8）、（1 487.4±174.4） U/L]显著下调（P＜0.05）,术后6h肝组织SOD活性E组（98.8±7.1）NU/g与B组（61.4±5.6）NU/g、C组（75.9±6.4） NU/g、D组（77.4±6.9） NU/g比较明显增强（P＜0.01）,病理改变明显减轻,Fasl基因（1.327±0.193）及蛋白表达（0.010 9 ±0.001 4）明显下调（P＜0.01）,Caspase-3蛋白表达水平（0.141 0 ±0.005 3）明显下调（P＜0.001）,β-catenin蛋白表达水平（0.079 1 ±0.008 2）明显上调（P＜0.01）.结论 异甘草酸镁联合维拉帕米能有效减轻肝切除肝缺血再灌注损伤.其对肝细胞的保护作用可能是抑制Fas/FasL系统介导的凋亡反应,上调3-catenin蛋白表达,促进肝脏再生,减轻肝脏过氧化损伤.
Objective To investigate protective effect of isoglycyrrhizinate combinated with verapamil on liver ischemia-reperfusion injury after semi-hepatectomy in rats.Methods Male SD rats were randomly divided into five groups：false operation （group A）;rats subjected to 50% hepatectomy and 45 min of hepatic ischemia （group B）;rats subjected to 50% hepatectomy and 45 min of hepatic ischemia,and treated with isoglycyrrhizinate （group C）;rats subjected to 50% hepatectomy and 45 min of hepatic ischemia,and treated with verapamil （group D）;rats subjected to 50% hepatectomy and 45 min of hepatic ischemia,and treated with isoglycyrrhizinate and verapamil （group E）.Liver function,as well as morphology,SOD activity,FasL,caspase 3,and β-catenin expression of rats were analyzed.Results Compared to group B,the levels of serum ALT of group E were significantly lower （P 〈 0.05）,SOD activity of liver tissue （98.8 ± 7.1） were significantly higher （P 〈 0.01）,pathological changes were milder,FasL gene （1.327 ±0.193） and protein （0.010 9 ±0.001 4） expression were significantly lower （P 〈0.01）.Caspase 3 protein expression levels （0.141 0 ±0.005 3） were significantly lower （P 〈0.001）,β-catenin protein expression levels （0.079 1 ± 0.008 2） were higher significantly （P 〈 0.01）.Conclusions Isoglycyrrhizinate combinated with verapamil can effectively reduce rats liver ischemia-reperfusion injury.The protective effect on liver cells may be mediated by inhibiting apoptosis caused by Fas/FasL system,increasing β-catenin protein expression,promoting liver regeneration and relieving liver peroxidation damage.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2015年第38期3119-3123,共5页
National Medical Journal of China
基金
中国肝炎防治基金会天晴肝病研究基金（CFHPC20132117）
关键词
异甘草酸镁
维拉帕米
大鼠
肝切除
肝缺血再灌注损伤
Isoglycyrrhizinate
Verapamil
Rats
Liver resction
Liver ischemia-reperfusion injury
