1.首都医科大学附属北京友谊医院国际医疗中心,北京 100050
2.首都医科大学基础医学院,北京 100069
孙晓静,女,35岁,博士,主治医师。研究方向:非酒精性脂肪性肝病的临床及基础研究。
李丽,E-mail:lili@ccmu.edu.cn
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孙晓静,孙凡淇,王亚宁,等.知母皂苷B-Ⅱ对非酒精性脂肪性肝病的治疗作用及机制研究[J].北京中医药,2023,42(6):636-642.
SUN Xiao-jing,SUN Fan-qi,WANG Ya-ning,et al.Effect and mechanism of Timosaponin B-Ⅱ on none alcoholic fatty liver disease in vitro and in vivo[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(06):636-642.
孙晓静,孙凡淇,王亚宁,等.知母皂苷B-Ⅱ对非酒精性脂肪性肝病的治疗作用及机制研究[J].北京中医药,2023,42(6):636-642. DOI: 10.16025/j.1674-1307.2023.06.012.
SUN Xiao-jing,SUN Fan-qi,WANG Ya-ning,et al.Effect and mechanism of Timosaponin B-Ⅱ on none alcoholic fatty liver disease in vitro and in vivo[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(06):636-642. DOI: 10.16025/j.1674-1307.2023.06.012.
目的,2,用体内外实验探讨知母皂苷B-Ⅱ(TB-Ⅱ)对非酒精性脂肪性肝病(NAFLD)的治疗作用及可能的作用机制。,方法,2,体外棕榈酸(100 μmol/L)处理人肝癌细胞(HepG2),同时加入不同浓度TB-Ⅱ干预24 h,检测细胞TG水平变化。将C75BL/6J小鼠随机分为正常饮食(NCD)组、高脂饮食(HFD)组、TB-Ⅱ低剂量组(HFD+LTB-Ⅱ)、TB-Ⅱ高剂量组(HFD+HTB-Ⅱ),NCD组喂以普通饲料,其余组均以高脂饲料喂养16周建立NAFLD动物模型,TB-Ⅱ低、高剂量组每天分别予50、100 mg/kgTB-Ⅱ灌胃;监测小鼠体质量、脂肪重量、生化指标及肝脏病理评估肝损伤程度,并通过实时定量PCR(RT-PCR)方法检测肝组织脂代谢相关基因变化。,结果,2,TB-Ⅱ处理后HepG2细胞TG水平下降;TB-Ⅱ治疗可使HFD小鼠体质量下降,血清转氨酶、TC、TG、LDL-C及肝组织TC和TG水平也显著下降,同时肝脏病理明显改善。其中脂质合成相关基因SREBP-1c、FAS及ACC1表达明显下降,并伴随脂肪酸β氧化关键基因CPT1、PPARα表达上调。,结论,2,TB-Ⅱ可通过调控肝细胞脂质合成及脂肪酸氧化延缓高脂诱导的NAFLD进程。
Objective,2,To explore the effects of Timosaponin B-Ⅱ (TB-Ⅱ) on non alcoholic fatty liver disease (NAFLD) and its mechanisms.,Methods,2,In vitro, HepG2 cells were stimulated with 100 μmol/L palmitate, without or with TB-Ⅱ and the changes of TG level were detected.In vivo, C57BL/6J mice were fed with normal diet group (NCD) , high-fat diet group (HFD), TB-Ⅱ low dose group (HFD+LTB-Ⅱ) and TB-Ⅱ high dose group (HFD+HTB-Ⅱ).The NCD group was fed with ordinary feed, the other groups were fed with high-fat feed for 16 weeks to establish NASH animal models, and the low and high-dose groups of TB-Ⅱ were gavaged with 50 mg/kg and 100 mg/kg respectively every day.The body weight, fat weight, biochemical indexes and liver pathology of mice were monitored to evaluate the degree of liver injury, and the changes of genes related to lipid metabolism in liver tissue were detected by real-time quantitative PCR(RT-PCR).,Results,2,TG level of HepG2 cellsTB-Ⅱ reduced after TB-Ⅱ treatment, TB-Ⅱ treatment can reduce the body weight of HFD mice,the levels of serum transaminase, TC, TG, LDL-C, TC and TG in liver tissue are also significantly decreased, and the liver pathology is obviously improved. but also downregulated the expression of lipogenesis-related genes (SREBP-1c, FAS and ACC) , accompanied by the up-regulation of the expression of key genes CPT1 and PPARα in fatty acid β oxidation.,Conclusion,2,TB-Ⅱ could delay the process of NAFLD induced by high fat by regulating lipid synthesis and fatty acid oxidation in hepatocytes.
非酒精性脂肪性肝病知母皂苷B-Ⅱ脂质代谢肝癌细胞小鼠
NAFLDTimosaponin B-Ⅱlipid metabolismmice
WESOLOWSKI SR, KASMI KC, JONSCHER KR, et al. Developmental origins of NAFLD: a womb with a clue[J]. Nat Rev Gastroenterol Hepatol,2017,14(2):81-96.
LOOMBA R, FRIEDMAN SL, SHULMAN GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease[J]. Cell, 2021,184(10):2537-2564.
FRIEDMAN SL, NEUSCHWANDER-TETRI BA, RINELLA M, et al. Mechanisms of NAFLD development and therapeutic strategies[J]. Nat Med, 2018,24(7):908-922.
张巍, 邵明亮, 苗同国,等. 清热利湿方对脂肪肝细胞磷脂肌醇-3激酶/肾上腺受体激酶表达的调节作用研究[J]. 北京中医药,2020,39(8):832-836,封3.
柯秀慧, 董瑞娟, 葛东宇,等. 慈姑多糖对非酒精性脂肪肝小鼠糖脂代谢的作用及机制[J]. 北京中医药,2019,38(7):644-649,封3.
DU MJ, CHEN JP, LIAN BW, et al. Cardioprotective effects of timosaponin B-Ⅱ isolated from Anemarrhena rhizome in a zebrafish model[J]. Pharmazie,2020,75(5):201-204.
XING N, WANG Y, WANG W, et al. Cardioprotective effect exerted by Timosaponin BⅡ through the regulation of endoplasmic stress-induced apoptosis[J]. Phytomedicine,2020,78:153288.
于晓彤, 刘文科. 仝小林运用纯中药治疗青少年2型糖尿病验案1则[J]. 北京中医药,2021,40(7):786-788.
PAI RK, JAIRATH V, HOGAN M, et al. Reliability of histologic assessment for NAFLD and development of an expanded NAFLD activity score[J]. Hepatology,2022,76(4):1150-1163.
陈润花, 谢春娥, 裴桂芳,等. 非酒精性脂肪性肝病中医证治探讨[J]. 北京中医药,2017,36(1):54-57.
LISTENBERGER LL, HAN X, LEWIS SE, et al. Triglyceride accumulation protects against fatty acid-induced lipotoxicity[J]. Proc Natl Acad Sci U S A,2003,100(6):3077-3082.
KOHJIMA M, ENJOJI M, HIGUCHI N, et al. Re-evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease[J]. Int J Mol Med, 2007,20(3):351-358.
YUAN YL, GUO CR, CUI LL, et al. Timosaponin B-II ameliorates diabetic nephropathy via TXNIP, mTOR, and NF-kappaB signaling pathways in alloxan-induced mice[J]. Drug Des Devel Ther,2015,9:6247-6258.
SANDERS FW, GRIFFIN JL. De novo lipogenesis in the liver in health and disease: more than just a shunting yard for glucose[J]. Biol Rev Camb Philos Soc,2016,91(2):452-468.
EBERLé D, HEGARTY B, BOSSARD P, et al. SREBP transcription factors: master regulators of lipid homeostasis[J]. Biochimie,2004,86(11):839-848.
HIGUCHI N, KATO M, SHUNDO Y, et al. Liver X receptor in cooperation with SREBP-1c is a major lipid synthesis regulator in nonalcoholic fatty liver disease[J]. Hepatol Res,2008,38(11):1122-1129.
LIANG G, YANG J, HORTON JD, et al. Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c[J]. J Biol Chem,2002,277(11):9520-9528.
SCHOELER M, CAESAR R. Dietary lipids, gut microbiota and lipid metabolism[J]. Rev Endocr Metab Disord,2019,20(4):461-472.
NASSIR F, IBDAH JA. Role of mitochondria in nonalcoholic fatty liver disease[J]. Int J Mol Sci,2014,15(5):8713-8742.
SCHLAEPFER IR, JOSHI M. CPT1A-mediated fat oxidation, mechanisms, and therapeutic potential[J]. Endocrinology,2020,161(2):bqz046.
FRANCQUE S, VERRIJKEN A, CARON S, et al. PPARα gene expression correlates with severity and histological treatment response in patients with non-alcoholic steatohepatitis[J]. J Hepatol,2015,63(1):164-173.
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