摘要
现代药理研究表明荒漠肉苁蓉具有肝保护作用,但其活性部位及作用机制并不清楚。为了明确荒漠肉苁蓉发挥肝保护作用的活性部位,本研究建立了急性酒精性肝损伤小鼠模型,并在此基础上对荒漠肉苁蓉的不同提取物部位(荒漠肉苁蓉总苷、荒漠肉苁蓉多糖和荒漠肉苁蓉寡糖)进行肝保护活性筛选。连续灌胃给药14天后,检测小鼠的肝脏病理结构及脂质沉积,并采用免疫荧光检测核因子E2相关因子(nuclear factor E2 related factors, Nrf-2)、胞质蛋白伴侣分子(kelch-like ECH-associated protein-1, Keap-1)及质膜囊泡相关蛋白1 (plasmalemma vesicle-associated protein-1, PV1)的蛋白表达,采用ELISA方法检测血清中谷丙转氨酶(alanine aminotransferase, ALT)、谷草转氨酶(aspartate aminotransferase, AST)、内毒素(endotoxin, ET)、二胺氧化酶(diamine oxidase, DAO)和D-乳酸(Dlactic acid, D-LA)含量,及肝脏中超氧化物歧化酶(superoxide dismutase, SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase, GSH-Px)及过氧化氢酶(catalase, CAT)活性和丙二醛(malondialdehyde, MDA)含量。动物实验操作和福利均遵循北京大学医学部实验动物伦理与动物福利委员会的规定。结果显示,与模型组相比,荒漠肉苁蓉总苷能够改善肝脏病理结构及降低肝脏中脂质沉积和血清中ET、DAO和D-LA含量。同时,荒漠肉苁蓉总苷能够促进Nrf-2入核并降低Keap-1和PV1表达。由此可见,荒漠肉苁蓉总苷在400 mg·kg^(-1)剂量下对急性酒精性肝损伤具有保护作用,其作用机制可能与激活Nrf-2/Keap-1通路和改善肠壁完整性有关。
Modern pharmacological studies have shown that Cistanche deserticola(C. deserticola) has a protective effect on the liver, but its active fraction and mechanism are not clear. In order to identify the effective fraction of C. deserticola Y. C. Ma, an acute alcoholic liver injury model in mice was established with 56-proof Erguotou and different fractional extracts of C. deserticola Y. C. Ma(total glycosides, polysaccharides, and oligosaccharides) were administered. After 14 days of oral administration, liver pathology and lipid deposition were measured and the expression of nuclear factor E2-related factor(Nrf-2), kelch-like ECH-associated protein-1(Keap-1), and plasmalemma vesicle-associated protein-1(PV1) were measured by immunofluorescence. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), endotoxin(ET), diamine oxidase(DAO),and D-lactic acid(D-LA) in serum, and superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), catalase(CAT), and malondialdehyde(MDA) in liver were measured by ELISA. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Peking University Health Science Center. The results show that the total glycosides of C. deserticola Y. C. Ma(400 mg·kg^(-1)) could decrease liver pathology, decrease serum endotoxin, diamine oxidase, and D-lactic acid, and reduce hepatic lipid deposition. Total glycosides also promoted Nrf-2 transfer into the nucleus and decreased the expression of Keap-1 and PV1. In summary, the total glycosides of C. deserticola Y. C. Ma had a protective effect in acute alcoholic liver injury and the mechanism may be related to the activation of the Nrf-2/Keap-1 pathway, improvement of intestinal wall integrity, and inhibition of the transport of harmful substances into the liver.
作者
王富江
屠鹏飞
曾克武
姜勇
WANG Fu-jiang;TU Peng-fei;ZENG Ke-wu;JIANG Yong(State Key Laboratory of Natural and Biomimetic Drugs,Peking University,Beijing 100191,China)
出处
《药学学报》
CAS
CSCD
北大核心
2021年第9期2528-2535,共8页
Acta Pharmaceutica Sinica
基金
国家重点研发计划(2017YFC1702402)
国家自然科学基金资助项目(81773932)。
关键词
肉苁蓉
酒精性肝损伤
荒漠肉苁蓉总苷
肝保护
Nrf-2/Keap-1通路
Cistanche deserticola Y.C.Ma
alcoholic liver disease
total glycosides of C.deserticola Y.C.Ma
liver protection
Nrf-2/Keap-1 pathway
作者简介
通讯作者:曾克武,Tel/Fax:86-10-82802719,E-mail:ZKW@bjmu.edu.cn;通讯作者:姜勇,E-mail:yongjiang@bjmu.edu.cn。
