摘要
目的:研究锰超氧化物歧化酶模拟化合物(Mn SODm)对四氯化碳(CCl_4)致小鼠急性肝损伤的保护作用,并初步探讨其作用机制。方法:将60只小鼠随机分为正常组、模型组、联苯双酯组(50 mg/kg)及Mn SODm低、中、高(10、20、40 mg/kg)剂量组。用CCl4建立小鼠急性肝损伤模型,检测小鼠血清与肝组织中谷丙转氨酶(ALT)与谷草转氨酶(AST)活力;并用苏木素-伊红(HE)染色处理肝脏组织切片,显微观察病理学改变;用试剂盒检测肝脏中超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性及谷胱甘肽过氧化物酶(GSH)含量; ELISA法检测小鼠肝脏中白介素-1β(IL-1β)、干扰素-γ(IFN-γ)水平。结果:在CCl_4诱导的小鼠肝急性损伤模型中,MnSODm能显著降低血清与肝组织中ALT、AST活力(P <0. 05或P <0. 01),明显改善肝脏病理组织状况; Mn SODm能显著降低小鼠肝组织中CAT活力和IL-1β、IFN-γ水平(P <0. 05或P <0. 01),同时显著增加SOD活力和GSH含量(P <0. 05或P <0. 01)。结论:MnSODm对CCl_4致小鼠急性肝损伤有明显的保护作用,其作用机制可能与其对抗和清除自由基、抑制炎症反应有关。
AIM: To investigate the effects of manganese superoxide dismutase mimic (MnSODm) on liver function and liver histological morphology in mice and to probe into its underlying mechanism. METHODS: Sixty mice were randomized into normal group, model group, bifendate group (50 mg/kg) and different doses of MnSODm (10, 20 and 40 mg/kg) group. Liver injury was induced by carbon tetrachloride (CCl4) in mice. The serum and liver activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. Liver tissue sections were examined under a light microscope. The activities of superoxide dismutase (SOD) and catcalase (CAT) and the level of glutathione (GSH) in liver homogenate were also detected. The contents of IL-1β, IFN-γ in liver homogenate were measured by ELISA. RESULTS: In the model of acute liver injury induced by CCl4 in mice, MnSODm markedly decreased the elevated serum and liver activities of ALT and AST. MnSODm effectively improved the tissue lesion of liver. In addition, MnSODm significantly increased SOD activity and GSH level (P<0.05 or P<0.01), and decreased activity of CAT and content of IL-1β, IFN-γ in liver (P<0.05 or P<0.01). CONCLUSION: The MnSODm has protective effect on acute liver injury induced by CCl4 in mice. The mechanism may be related to inhibition of oxidative stress and inflammatory reaction.
作者
王艳红
冯铁新
蒲君峰
张玲芳
李红玲
WANG Yanhong;FENG Tiexin;PU Junfeng;ZHANG Lingfang;LI Hongling(Department of Pharmacy,Gansu Provincial Hospital,Lanzhou 730000,Gansu,China;Outpatient Department of Xiaoxitian,309Hospital of the Chinese PLA,Agency for Offices Administration of the Central Military Commission,Beijing 100082,China;Division of Oncology,Gansu Provincial Hospital,Lanzhou 730000,Gansu,China)
出处
《中国临床药理学与治疗学》
CAS
CSCD
2018年第11期1209-1214,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家自然科学基金项目(81560498)
关键词
锰超氧化物歧化酶模拟化合物
四氯化碳
肝损伤
保护作用
manganese superoxide dismutase mimic
carbon tetrachloride
liver injury
protective effects
