右美托咪定联合扶正化瘀方对顺铂诱导的氧化性肝损伤的保护作用  

Protective effect of dexmedetomidine combined with Fuzheng Huayu recipe on oxidative liver injury induced by cisplatin

作　　者：李延玲[1] 陆蒂青[1] 李金妞 郭杰 夏盼盼 卢瑞杰[1] 霍丽亚[1] 孙长宇[4] LI Yan-ling;LU Di-qing;LI Jin-niu;GUO Jie;XIA Pan-pan;LU Rui-jie;HUO Li-ya;SUN Chang-yu(The Centre Hospital of Nanyang,Nanyang Henan 473009,China;Hanyang Hospital of Traditional Chinese Medicine,Nanyang Henan 473000,China;The First Affiliated Hospital of Hanyang Medical College,Nanyang Henan 473000,China;First Affiliated Hospital of Zhengzhou University,Zhengzhou Henan 450052,China)

机构地区：[1]南阳市中心医院,河南南阳473009 [2]南阳市中医院,河南南阳473000 [3]南阳医专第一附属医院,河南南阳473000 [4]郑州大学第一附属医院,河南郑州450052

出　　处：《毒理学杂志》2021年第1期67-71,76,共6页Journal of Toxicology

摘　　要：目的探索右美托咪定(Dexmedetomidine,DEX)联合扶正化瘀方对顺铂诱导的氧化性肝损伤的保护作用机制。方法SD大鼠腹腔注射顺铂5 mg/kg·bw的方法制备氧化性肝损伤动物体内模型,分为5组:正常组、模型组、DEX组、扶正化瘀方组和联合组(DEX和扶正化瘀方联合用药组);分别腹腔注射处理10 d,眼眶采血酶联免疫吸附法(ELISA)检测血清中肝功能指标丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平;处死后检测肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)及谷胱甘肽转移酶(GSH-Px)含量。运用5 mg/ml顺铂处理大鼠肝BRL细胞制备氧化性肝损伤体外模型,分为5组:正常组、顺铂组(顺铂诱导的大鼠肝BRL细胞损伤组)、DEX组、扶正化瘀方组和联合组;采用MTT法检测细胞存活率;流式细胞术检测模型细胞的凋亡率;采用蛋白质印迹法(Western blot)检测细胞中凋亡相关蛋白Bax和Bcl-2的表达情况;采用ELISA检测SOD、GSH-Px活性和MDA含量。结果构建了顺铂诱导的氧化性肝损伤大鼠动物模型,与模型组相比,DEX组、扶正化瘀方组和联合组血清中ALT和AST均明显下降(P<0.05),肝组织中SOD和GSH-Px明显升高(P<0.05),MDA明显降低(P<0.05);且联合组相较单独用药组和模型组升高或下降幅度最大,差异有统计学意义(P<0.05)。构建了顺铂诱导的氧化性肝损伤大鼠肝BRL细胞模型,联合组细胞存活率为83.09%,明显高于单独给药组和顺铂组(P<0.05);联合组中顺铂诱导的BRL肝细胞凋亡率为8.50%,其中凋亡蛋白Bax表达明显下调(P<0.05),抗凋亡蛋白Bcl-2的表达上调(P<0.05),SOD和GSH-Px升高(P<0.05),MDA降低,差异均有统计学意义(P<0.05)。结论DEX联合扶正化瘀方可增强肝细胞活力、抑制肝细胞凋亡和降低氧化应激反应,对顺铂诱导的氧化性肝损伤有一定的保护作用。Objective To explore the protective mechanism of Dexmedetomidine(DEX)combined with Fuzheng Huayu recipe on cisplatin-induced oxidative liver injury.Methods SD rats were given intraperitoneal injection of cisplatin 5 mg/kg·bw to prepare animal models of oxidative liver injury,which were divided into five groups:normal group,model group,dexmedetomidine group,Fuzheng Huayu prescription group and combination group(Dexmedetomidine and Fuzheng Huayu recipe combined medication group);treated by intraperitoneal injection for 10 days,Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of liver function indicators alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum;After execution,the contents of superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione transferase(GSH-Px)in liver tissues were detected.The in vitro model of oxidative liver injury was prepared by treating BRL cells of rat liver with 5 mg/ml cisplatin,which was divided into five groups:normal group,cisplatin group(cisplatin-induced rat liver BRL cell injury group),dexmedetomidine group,Fuzheng Huayu recipe group and combination group;MTT method was used to detect cell survival rate;flow cytometry was used to detect the apoptosis rate of model cells;Western blot was used to detect the expressions of apoptosis-related proteins Bax and Bcl-2.The expressions of SOD,GSH-Px activity and MDA content were detected by ELISA.Results An animal model of cisplatin-induced oxidative liver injury in rats was constructed.Compared with the model group,the serum ALT and AST in the dexmedetomidine group,the Fuzheng Huayu prescription group and the combination group were significantly decreased(P<0.05),SOD and GSH-Px in liver tissue were significantly increased(P<0.05),and MDA was significantly reduced(P<0.05);and the combination group had the largest increase or decrease compared with the single medication group and the model group(P<0.05).A cisplatin-induced oxidative liver injury rat liver BRL cell model was constructed.The cell su

关 键 词：右美托咪定 扶正化瘀方 顺铂 联合用药 肝损伤 

分 类 号：R114[医药卫生—卫生毒理学] R965[医药卫生—公共卫生与预防医学]