四味护肝饮对D-半乳糖胺致小鼠肝损伤的预防作用及相关机制  

The protective effect and mechanism of Siwei Hugan Decoction on D-galactosamine-induced liver injury in mice

作　　者：张一凡 李怡萍 刘洋 周岐鸣 唐志鹏 宋海燕 ZHANG Yifan;LI Yiping;LIU Yang;ZHOU Qiming;TANG Zhipeng;SONG Haiyan(Institute of Digestive Diseases,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032 China;China-Canada Centre of Research for Digestive Diseases,Shanghai 200032,China)

机构地区：[1]上海中医药大学附属龙华医院脾胃病研究所,上海200032 [2]中加联合脾胃病研究中心,上海200032

出　　处：《暨南大学学报（自然科学与医学版）》2022年第2期122-128,共7页Journal of Jinan University(Natural Science & Medicine Edition)

基　　金：国家自然科学基金项目(81703867,81573894);上海市中医药新兴交叉学科资助计划;上海中医药大学研究生“创新能力培养”专项科研项目。

摘　　要：目的:研究中药复方四味护肝饮对肝损伤的药物效应,并初步探讨其药物作用机理。方法:C57BL/6J小鼠24只,按照体质量随机分为4组:正常组(CON)、模型组(MOD)、四味护肝饮组(SHD)、美能组(CG),每组6只。SHD组、CG组小鼠每天予以相应药物灌胃,CON组与MOD组予等体积的0.9%氯化钠溶液灌胃,持续10 d。在末次给药1 h后,除正常组外,其余各组分别予以腹腔注射800 mg·kg;的D-半乳糖胺溶液(D-Gal N)以诱导小鼠急性肝损伤。在注射D-Gal N 24h后,处死小鼠并收取血清及肝组织。检测小鼠肝组织病理、血清转氨酶的改变,并检测肝组织IL-1β、TNF-α、A20表达水平,以及NF-κB活化水平。结果:MOD组小鼠肝组织出现炎性细胞浸润提示急性肝损伤模型构建成功。与MOD组比较,CG组和SHD组小鼠肝组织炎性浸润显著减轻。与CON组比较,MOD组小鼠血清ALT、AST、LDH显著升高,肝组织IL-1β和TNF-α的mRNA、蛋白表达上调,肝组织A20表达有上调趋势,p-NF-κB蛋白表达水平显著升高(P<0.05);与MOD组比较,四味护肝饮干预显著降低AST、LDH含量及肝组织TNF-αmRNA、IL-1β和TNF-α蛋白表达,上调A20蛋白表达,下调p-NF-κB蛋白水平(P<0.05)。与MOD组比较,美能可显著降低血清ALT、AST、LDH及肝组织炎性细胞因子表达、p-NF-κB水平,上调A20蛋白表达(P<0.05)。结论:四味护肝饮可减轻D-Gal N诱导的小鼠急性肝损伤,上调A20表达从而抑制NF-κB活化,可能是其发挥药效作用的部分机制。Objective:This study aimed to investigate the effect of Siwei Hugan Decoction on reducing the inflammation in liver damage caused by viral hepatitis. Methods: Totally 24 C57 BL/6 mice were randomly divided into 4 groups: control group(CON), model group(MOD), Compound Glycyrrhizin(CG)group and Siwei Hugan Decoction(SHD) group, with 6 mice in each group. The mice in the SHD group and the CG group were given the corresponding medicine every day. CON group and MOD group were given a corresponding volume of 0.9% sodium chloride solution. The administration was lasted for 10 days. 1 hour after the last administration, except CON group, the other groups were intraperitoneally injected with 800 mg/kg of D-galactosamine(D-Gal N) solution to induce acute liver injury. 24 hours after D-Gal N injection, serum and liver tissue were collected. The pathological changes of liver tissue, serum transaminase, the mRNA and protein levels of IL-1β, TNF-α, A20 and NF-κB in liver tissues were detected. Results: MOD group had inflammatory cell infiltration. The inflammation of liver were significantly reduced in the CG group and SHD group compared with that in MOD group. The serum level of ALT, AST and LDH,the mRNA and protein expression of IL-1β, TNF-αand the protein level of p-NF-κB in MOD mice were significantly increased(P<0.05). The SHD significantly decreased the level of AST and LDH, the mRNA expression of TNF-α, and the protein expression of IL-1β, TNF-α and p-NF-κB. SHD significantly up-regulated the expression of A20 protein(P<0.05). The serum levels of ALT, AST and LDH, the expression of inflammatory cytokines, and p-NF-κB protein expression in the CG group were significantly lower. The CG also significantly increased A20 protein expression(P<0.05). Conclusion:SHD can ameliorate liver damage by up-regulation of A20 and decreasing NF-κB activation in mice with acute liver injury.

关 键 词：急性肝损伤 病毒性肝炎 四味护肝饮 锌指蛋白A20 

分 类 号：R259[医药卫生—中西医结合]