异甘草酸镁在HBV转基因小鼠中的药效学研究  

Pharmacodynamic study of magnesium isoglycyrrhizinate in HBV transgenic mouse model

作　　者：徐宏江 施伟 宋伟 张颖 赵凯迪 张寅生 杨玲 汪纪楠 XU Hongjiang;SHI Wei;SONG Wei;ZHANG Ying;ZHAO Kaidi;ZHANG Yinsheng;YANG Ling;WANG Jinan(Research Institute of Chia Tai Tianqing Pharmaceutical Group Co.,Ltd.,Jiangsu Key Laboratory of Targeted Antiviral Drug Research,Nanjing 210042,China)

机构地区：[1]正大天晴药业集团股份有限公司研究院江苏省抗病毒靶向药物研究重点实验室

出　　处：《中国药科大学学报》2019年第4期475-480,共6页Journal of China Pharmaceutical University

基　　金：江苏省抗病毒靶向药物研究重点实验室资助项目(No.SBM2016200031);江苏省“六大人才高峰”高层次人才培养资助项目(No.2016-SWYY-199)~~

摘　　要：探讨异甘草酸镁对乙型肝炎病毒(HBV)转基因小鼠的治疗作用及对细胞免疫和肝脏炎症的影响。通过检测两组小鼠血清天门冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)活性的变化,血清乙肝表面抗原(HBsAg)、肝脏组织HBsAg mRNA的差异以及肝脏组织的病理形态学变化考察HBV转基因小鼠的肝脏炎性病变和异甘草酸镁的药效。利用流式细胞术进行外周血淋巴细胞分群以及流式细胞小球微阵列术(CBA)检测血清细胞因子,探索异甘草酸镁减轻HBV转基因小鼠肝脏炎性病变的作用机制。结果表明,以血清转氨酶活性将HBV转基因小鼠分组后,连续给药35 d,异甘草酸镁组[15 mg/(kg·d)]小鼠血清转氨酶水平显著低于对照组(P<0.05);血清HBsAg蛋白和肝脏组织HBsAg mRNA均随时间延长而升高,但两组间无显著差异;肝脏的主要病理改变为肝细胞肿胀、坏死和局灶性炎细胞浸润,异甘草酸镁组小鼠的肝脏病理形态学改变轻于对照组。异甘草酸镁组小鼠血液中CD8+细胞数量显著少于对照组(P<0.05),CD4^+/CD8^+细胞比例显著高于对照组(P<0.05);异甘草酸镁组小鼠血清中促炎细胞因子含量显著降低(P<0.05)。本研究表明,异甘草酸镁可以调节HBV转基因小鼠的免疫功能,减少肝组织炎性细胞浸润和肝细胞损伤,但不影响肝细胞HBsAg表达。This study aims to discuss the therapeutic effect of magnesium isoglycyrrhizinate on hepatitis B virus(HBV)transgenic mouse and its effect on cellular immunity and liver inflammation.The changes of serum aspartate aminotransferase(AST)and alanine aminotransferase(ALT)activity,the difference of serum hepatitis B surface antigen(HBsAg),liver tissue HBsAg mRNA,and the pathological morphological changes of liver tissue were detected to investigate the hepatic inflammatory lesions and the efficacy of magnesium isoglycyrrhizinate in HBV transgenic mouse.Peripheral blood lymphocytes were classified by flow cytometry,and serum cytokines were detected by cytometric bead array(CBA)to explore the mechanism of magnesium isoglycyrrhizinate to reduce hepatic inflammatory lesions in HBV transgenic mouse.After grouping HBV transgenic mouse with serum transaminase activity and 35 days of continuous administration,serum transaminases level in magnesium isoglycyrrhizinate[15 mg/(kg·d)]group was significantly lower than that in control group(P<0.05),serum HBsAg protein and liver tissue HBsAg mRNA increased with time,but there was no significant difference between the two groups.The main pathological changes of liver were liver cell swelling,necrosis and focal inflammatory cell infiltration,and the pathological changes of liver in magnesium isoglycyrrhizinate group were lighter than those in control group.The number of CD8^+cells in the blood of magnesium isoglycyrrhizinate group was significantly less than that in the control group(P<0.05)and the CD4^+/CD8^+cell ratio was significantly higher than that in the control group(P<0.05).The content of inflammatory cytokines in serum of magnesium isoglycyrrhizinate group decreased significantly(P<0.05).Magnesium isoglycyrrhizinate can regulate the immune function of HBV transgenic mouse,decrease the infiltration of inflammatory cells in hepatic tissue and hepatocyte injury,but do not affect the expression of hepatocyte HBsAg.

关 键 词：异甘草酸镁 乙型肝炎 转基因小鼠 免疫调节 

分 类 号：R965[医药卫生—药理学]