淫羊藿苷对四氯化碳诱导小鼠急性肝损伤的保护作用机制  

Protective effect and mechanism of icariin against carbon tetrachloride-induced acute liver injury in mice

作　　者：肖冬焱 何伟 肖志滢 廖月 毛家豪 何毅怀 蒋智钢 Xiao Dongyan;He Wei;Xiao Zhiying;Liao Yue;Mao Jiahao;He Yihuai;Jiang Zhigang(Zunyi Medical and Pharmaceutical College,Zunyi 563000,Guizhou Province,China;Zunyi Medical University,Zunyi 563000,Guizhou Province,China;Department of Infectious Diseases,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,Guizhou Province,China)

机构地区：[1]遵义医药高等专科学校,贵州省遵义市563000 [2]遵义医科大学,贵州省遵义市563000 [3]遵义医科大学附属医院感染科,贵州省遵义市563000

出　　处：《中国组织工程研究》2024年第23期3654-3660,共7页Chinese Journal of Tissue Engineering Research

基　　金：遵义市科技计划项目[遵市科合HZ字(2019)199号],项目负责人:肖冬焱;遵义市科技计划项目[遵市科合HZ字(2021)224号],项目负责人:肖冬焱;贵州省科技计划项目(黔科合基础-ZK[2022]一般642)(QKHJC-ZK[2022]YB642),项目负责人:何毅怀。

摘　　要：背景:淫羊藿苷具有抗炎、抗氧化、免疫调节等功能,可能成为预防和治疗急性肝损伤的潜在药物。目的:分析淫羊藿苷对四氯化碳诱导小鼠急性肝损伤的保护作用及可能机制。方法:取32只昆明小鼠,采用随机数字表法分为正常组、模型组、淫羊藿苷低剂量组及淫羊藿苷高剂量组,每组8只。正常组、模型组灌胃给予10 mL/kg的生理盐水,淫羊藿苷低剂量组、淫羊藿苷高剂量组分别灌胃给予100,200 mg/kg的淫羊藿苷混悬液,1次/d,连续7 d。末次给药后,模型组、淫羊藿苷低剂量组及淫羊藿苷高剂量组通过腹腔注射四氯化碳建立急性肝损伤模型,造模24 h后,检测小鼠肝指数与血清中丙氨酸氨基转移酶、天冬氨酸氨基转移酶、肿瘤坏死因子α及白细胞介素6水平,肝组织中超氧化物歧化酶、谷胱甘肽过氧化物酶及丙二醛浓度,肝组织病理形态及肝细胞凋亡情况,以及肝组织中混葡萄糖调节蛋白78、内质网应激相关蛋白、混合谱系激酶域样蛋白及Caspase-3的蛋白表达。结果与结论:①与正常组比较,模型组小鼠肝指数与血清中丙氨酸氨基转移酶、天冬氨酸氨基转移酶、肿瘤坏死因子α及白细胞介素6水平均升高(P均<0.05);与模型组比较,淫羊藿苷低剂量组、淫羊藿苷高剂量组小鼠上述指标均降低(P均<0.05);②与正常组比较,模型组小鼠肝组织中超氧化物歧化酶、谷胱甘肽过氧化物酶活性降低(P均<0.05),丙二醛水平升高(P<0.05);与模型组比较,淫羊藿苷低剂量组、淫羊藿苷高剂量组小鼠超氧化物歧化酶、谷胱甘肽过氧化物酶活性升高(P均<0.05),丙二醛水平降低(P<0.05);③苏木精-伊红与TUNEL染色显示,模型组小鼠肝组织结构破坏严重,肝细胞大面积坏死,肝细胞凋亡率较高;淫羊藿苷低剂量组及淫羊藿苷高剂量组小鼠肝组织结构破坏程度及肝细胞坏死面积明显轻于模型组,肝细胞凋亡率低于模型组(BACKGROUND:Icariin,with antiinflammatory,antioxygenatory and immunoregulatory effects,can be a potential drug for preventing and treating acute liver injury.OBJECTIVE:To investigate the protective effect and possible mechanism of icariin in mice with acute liver injury induced by carbon tetrachloride.METHODS:Thirty-two Kunming mice were equally and randomly divided into the following groups:normal,model,low-dose icariin and high-dose icariin groups.The low-and high-dose icariin groups were continuously gavaged with icariin(100 and 200 mg/kg,respectively)once a day for 7 continuous days.The normal group and model group were injected with physiological saline(10 mL/kg)at the same time point.After the last administration,all the groups except for the normal group were injected with carbon tetrachloride to induce acute liver injury.The mice were killed 24 hours later,and the liver index was detected.Serum levels of alanine aminotransferase and aspartate aminotransferase were detected by automated biochemical analysis.Tumor necrosis factorαand interleukin 6 levels in serum were detected using ELISA.The levels of superoxide dismutase,glutathione peroxidase and malondialdehyde in liver tissue were detected through a reagent kit.The histopathology changes of the liver were observed by hematoxylin-eosin staining.TUNEL method was used to detect the apoptosis in hepatocytes.Western blot was performed to detect the expression levels of glucose-regulated protein 78 kDa,endoplasmic reticulum stressrelated protein(C/-EBP homologous protein),mixed lineage kinase domain-like protein and Caspase-3 in liver tissue.RESULTS AND CONCLUSION:Compared with the normal group,the liver index and serum levels of alanine aminotransferase,aspartate aminotransferase,tumor necrosis factorαand interleukin 6 were increased in the model group(P<0.05).Compared with the model group,the above indexes were decreased in the low-dose and high-dose icariin groups(P<0.05).Compared with the normal group,the activities of superoxide dismutase and glutathio

关 键 词：淫羊藿苷 急性肝损伤 抗炎 抗氧化 内质网应激 程序性坏死 

分 类 号：R459.9[医药卫生—治疗学] R313[医药卫生—临床医学] R285.5