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2021, v.31(06) 409-415+469

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甜菜提取物及复方对化学性肝损伤的保护作用研究
Study on the Protective Effects of Beet Extract and Beet-Schisandra Extract Compound on CCl_4-induced Liver Injury

马佳琪;龚海标;李娥;丁肇俊;孙万阳;段文君;梁磊;何蓉蓉;
MA Jiaqi;GONG Haibiao;LI E;DING Zhaojun;SUN Wanyang;DUAN Wenjun;LIANG Lei;HE Rongrong;International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE),College of Pharmacy,Jinan University;Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research,College of Pharmacy,Jinan University;Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibility,College of

摘要(Abstract):

目的研究甜菜提取物及甜菜五味子复方对四氯化碳(CCl_4)化学性肝损伤的保护作用。方法小鼠随机分为正常对照组、CCl_4模型组、甜菜提取物低、中、高剂量组(1.5, 3, 6 g·kg~(-1) BW)、甜菜五味子复方组(1.67 g·kg~(-1) BW)和水飞蓟素阳性对照组(150 mg·kg~(-1) BW),各组动物灌胃给药30 d后观察其对四氯化碳肝损伤模型小鼠的保护作用。记录小鼠肝脏外观形态并检测肝指数;试剂盒检测小鼠血清谷草转氨酶(AST)和谷丙转氨酶(ALT)的水平,组织切片HE染色观察小鼠肝脏病理改变;LC-MS检测小鼠血浆中甜菜碱(Betaine)及其代谢物N,N-二甲基甘氨酸(DMG)的水平。机制研究实验中,小鼠随机分为空白对照组、CCl_4模型组、甜菜碱500 mg·kg~(-1)给药组,给药与造模方法同上,采用试剂盒检测肝脏中丙二醛(MDA)和谷胱甘肽(GSH)的含量,Western blot检测肝脏4-羟基壬烯醛(4-HNE)及15-脂氧合酶(15-LOX)的表达。结果甜菜提取物各剂量和甜菜五味子复方均能显著降低肝损伤小鼠的肝指数,降低血清AST和ALT的水平,缓解小鼠肝脏组织病理改变。复方组小鼠血浆中Betaine和DMG的水平明显高于单纯甜菜提取物组。Betaine给药可提高肝脏GSH的水平,降低小鼠肝脏MDA的含量以及4-HNE和15-LOX的蛋白表达。结论甜菜提取物及甜菜五味子复方对化学性肝损伤均具有保护作用;复方中五味子可促进甜菜碱的吸收,增强甜菜提取物的护肝作用;甜菜碱可能通过降低15-LOX的表达缓解脂质过氧化造成的肝损伤。
OBJECTIVE To study the protective effects of beet extract(BE)and beet and Schisandra extract compound(BEC)on CCl_4-induced liver injury. METHODS Mice were randomly divided into control group, CCl_4 group, the low, medium and high dose of BE groups(1.5,3 and 6 g·kg~(-1) BW),BEC group(1.67 g·kg~(-1) BW)and Silymarin group(150 mg·kg~(-1) BW).The mice except control group were induced liver injury by CCl_4 then administrated with the corresponding treatment daily by gavage for 30 days.The livers were observed and collected to weigh.The liver index was calculated.The levels of serum aspartate aminotransferase(AST),alanine aminotransferase(ALT)were detected by detection kits.Tissue sections and HE staining were employed for observation of the pathological changes of livers.Betaine and its metabolite N,N-dimethylglycine(DMG)in plasma were determined by LC-MS.In another experiment, mice were randomly divided into control group, CCl_4 group and Betaine group(500 mg·kg~(-1))to study the possible mechanism.Malondialdehyde(MDA)and glutathione(GSH)in livers were detected by detection kits.Western blot was used to detect the expression of 4-hydroxynonenal(4-HNE)and 15-lipoxygenase(15-LOX)in livers. RESULTS All groups of BE and BEC reduced the liver indexes of mice and the levels of serum AST and ALT,and alleviated liver injury in mice notably.The levels of betaine and DMG in the plasma in BEC group were significantly higher than those in BE group.Betaine increased the level of GSH in the livers, and reduced the content of MDA.In addition, the expressions of 4-HNE and 15-LOX in the livers decreased in Betaine group. CONCLUSION Both BE and BEC have protective effects on CCl_4-induced liver injury in mice.Schisandra could enhance the hepatoprotective effect of BE by promoting the absorption of betaine in blood.Reduction of 15-LOX may be involved in the mechanism of betaine relieving lipid peroxidation in liver injury.

关键词(KeyWords): 甜菜提取物;甜菜碱;五味子;肝损伤;四氯化碳;15-脂氧合酶
beet extract;betaine;Schisandra;liver injury;CCl_4;15-lipoxygenase

Abstract:

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基金项目(Foundation): 广东省自然科学基金(No.2021A1515011297)

作者(Author): 马佳琪;龚海标;李娥;丁肇俊;孙万阳;段文君;梁磊;何蓉蓉;
MA Jiaqi;GONG Haibiao;LI E;DING Zhaojun;SUN Wanyang;DUAN Wenjun;LIANG Lei;HE Rongrong;International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE),College of Pharmacy,Jinan University;Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research,College of Pharmacy,Jinan University;Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibility,College of

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