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作 者:仲金秋 曹玉珠[1] 徐宏江 吴媛媛 张婷婷[1] 李晓曼 陈文星[1,3] 王爱云[1,3] 陆茵[1,3] ZHONG Jin-qiu;CAO Yu-zhu;XU Hong-jiang;WU Yuan-yuan;ZHANG Ting-ting;LI Xiao-man;CHEN Wen-xing;WANG Ai-yun;LU Yin(Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica,School of Pharmacy,Nanjing University of Chinese Medicine;Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor,Nanjing University of Chinese Medicine;Institute for Pharmacology & Toxicology,Chia Tai Tianqing Pharmaceutical Group Co.,LTD,Nanjing 210023 ,China)
机构地区:[1]南京中医药大学江苏省中药药效与安全性评价重点实验室 [2]中国药理学与毒理学研究所正大天晴药业集团股份有限公司,南京210023 [3]南京中医药大学江苏省中医药防治肿瘤协同创新中心
出 处:《天然产物研究与开发》2018年第12期2088-2096,共9页Natural Product Research and Development
基 金:江苏省自然科学基金(BK20141243);江苏高校品牌专业建设工程(PPZY2015A070);江苏省重点实验室开放项目(JKLPSE201602);江苏省中药药效与安全性评价重点实验室资助项目(JKLPSE201610);江苏高校中药学优势学科建设工程(PAPD)[苏政办发(2014)37号文]
摘 要:探讨甘草酸二铵(Diammonium glycyrrhi zinate,DG)对刀豆蛋白(Concanavalin A,Con A)致小鼠肝损伤的保护作用及机制。连续给予ICR小鼠各保肝药的临床等效量7天后,再以Con A造成小鼠肝损伤。生化法检测血清中谷草转氨酶(AST)、谷丙转氨酶(ALT)含量;HE染色观察肝组织病理学特征;通过药物代谢物与转氨酶异常大鼠血清共孵育,检测DG对转氨酶活性的直接作用;免疫组化、Western blot检测肝组织中凋亡蛋白和炎性细胞因子的水平,探讨DG的保肝机制。结果显示,58. 5 mg/kg DG能够改善Con A所致小鼠肝脏病理损伤,降低小鼠血清中AST、ALT水平,而对AST、ALT的活性没有直接抑制作用;并且DG可以抑制肝细胞凋亡(下调cleaved Caspase-3、cleaved PARP以及BAX/BCL-2的表达)和炎性反应(降低TGF-β1、COX-2、IL-6、TNF-α和IFN-γ等炎性因子水平)。综上所述,DG可改善Con A致小鼠急性肝损伤,其作用机制可能与抑制细胞凋亡和炎症反应有关。This study was to investigate the effect and the underlying mechanism of DG on the hepatotoxicity induced by Con A.In this study,a concanavalin A(Con A)-induced hepatitis mouse model was used to examine the effect of DG on hepatic injury.DG(58.5mg/kg),silymarin(36.4mg/kg)and bicyclol(9.75mg/kg)equivalent to clinical dosage were orally administered to mice once daily for7consecutive days before Con A challenge.After that,blood samples were collected for serological detection,and histological analysis was carried out by hematoxylin-eosin staining.In order to investigate the molecular mechanism of DG’s protective effect,the serum-drug incubation assay,immunohistochemistry and western blot were conducted.Hematoxylin-eosin staining showed that DG pre-treatment prevented Con A-induced liver structural damage in ICR mice.We also observed the reduced serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities.However,the serum-drug incubation assay indicated that DG cannot directly attenuate ALT and AST levels.Meanwhile,experimental results proved that DG pretreatment down-regulates cleaved Caspase-3,cleaved PARP,ratio of BAX/BCL-2expression level and expression of TGF-β1,COX-2,IL-6,TNF-α,IFN-γinflammatory mediators.Taken together,DG can inhibit Con A-induced hepatic injury by inhibition of apoptosis and inflammation.
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