甘草酸制剂对阿霉素所致小鼠心脏及肝脏损伤的抑制作用研究

Inhibitory Effect of Glycyrrhizic Acid Preparation on Cardiac and Liver Injury Induced by Adriamycin in Mice

目的分析甘草酸制剂对阿霉素(ADM)所致小鼠心脏、肝脏损伤的抑制作用及机制。方法选择小鼠60只,按随机数字表法分为正常对照组、ADM组、异甘草酸镁(MgIG)组,每组20只。MgIG组给予MgIG(40 mg/kg)腹腔注射,连续10日;第8日下午MgIG组、ADM组给予ADM(30 mg/kg)腹腔注射,正常对照组给予等体积生理盐水腹腔注射;第10日下午股动脉采血,离心后取血清,经全自动生化分析仪检测肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、AST、ALT水平,利用试剂盒计算出超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力及丙二醛(MDA)含量,取心脏、肝脏组织进行Bax、Bcl-2、Caspase-3、NF-κB p65蛋白Western Blot检测及凋亡细胞的TUNEL检测。结果与正常对照组比较,ADM组小鼠血清CK、CK-MB、LDH、AST、ALT、MDA水平升高(P<0.01),SOD、GSH-Px水平降低(P<0.01),心脏、肝脏组织中Bax/Bcl-2、Caspase-3、NF-κB p65蛋白表达升高(P<0.01),小鼠心脏、肝脏组织中TUNEL阳性细胞明显增加。与ADM组比较,MgIG组小鼠血清CK、CK-MB、LDH、AST、ALT、MDA水平降低(P<0.01),SOD、GSH-Px水平升高(P<0.01),心脏、肝脏组织中Bax/Bcl-2、Caspase-3、NF-κB p65蛋白表达降低(P<0.01),小鼠心脏、肝脏组织中TUNEL阳性细胞数量减少(P<0.01)。结论甘草酸制剂对ADM所致小鼠心脏、肝脏损伤具有明显的抑制作用,其可能与增强心肌及肝细胞的抗氧化能力和抑制凋亡有关。

Objective To analyze the inhibitory effect and mechanism of glycyrrhizic acid preparation on adriamycin(ADM)-induced heart and liver injury in mice.Methods A total of 60 mice were selected and randomly divided into normal control group,ADM group and magnesium isoglycyrrhizinate(MgIG)group by random number table,with 20 mice in each group.MgIG group was intraperitoneally injected with MglG(40 mg/kg)every morning for 10 consecutive days.On the afternoon of the 8 th day,MgIG group and ADM group were intraperitoneally injected with ADM(30 mg/kg),and the normal control group was intraperitoneally injected with the equal volume of saline.The femoral artery blood were harvested on the afternoon of the 10 th day.The sera samples were collected and purified by centrifugation.The levels of creatine kinase(CK),creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),AST and ALT were detected by automatic biochemical analyzer.The activity of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)and the content of MDA were calculated with the kit.The proteins of Bax,Bcl-2,Caspase-3 and NF-κB p65 were detected by Western Blot,and apoptotic cells were detected by TUNEL.Results Compared with the normal control group,the serum levels of CK,CK-MB,LDH,AST,ALT and MDA in ADM group were increased(P<0.01),and SOD and GSH-Px levels decreased(P<0.01).Bax/Bcl-2,Caspase-3,NF-κB p65 protein expression in the heart and liver tissues were increased(P<0.01),and TUNEL positive cells were significantly increased in the heart and liver tissues of mice.Compared with ADM group,serum levels of CK,CK-MB,LDH,AST,ALT and MDA were decreased in MgIG group(P<0.01),and SOD and GSH-PX levels increased(P<0.01).Bax/Bcl-2,Caspase-3 and NF-κB p65 protein expression in heart and liver tissues were decreased(P<0.01),and the TUNEL positive cells in heart and liver tissues were decreased(P<0.01).Conclusions Glycyrrhizic acid preparation has obvious protective effect on the injury of heart and liver caused by ADM in mice,and its mechanism might be related to the enhancement of antioxidant capacity and inhibition of apoptosis in myocardium and hepatocytes.