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Issue:ISSN 1000-7083
          CN 51-1193/Q
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Your Position :Home->Past Journals Catalog->2016 Vol.35 No.4

The Effects of Betulinic Acid on the Expression of Cytokines and Apoptosis-related Proteins in Immune Liver Injury Induced by Concanavalin A
Author of the article:WANG Baili1,3, WU Huantong1,2, CAO Chang1,2, ZHANG Shuping1,2*, QIN Xiaoyan1,2*
Author's Workplace:1. College of Life & Environmental Science, Minzu University of China, Beijing 100081, China;
2. Beijing Engineering Research Center of Food Environment and Health, Minzu University of China, Beijing 100081, China;
3. The School Hospital Clinical Laboratory, Minzu University of China, Beijing 100081, China
Key Words:betulinic acid; concanavalin A; acute immune liver injury; cytokines; Bcl-2; activated-Caspase-3
Abstract:Objective To study the effects of betulinic acid (BA) on the expression of cytokines and apoptosis-related proteins in acute immune liver injury induced by concanavalin A (Con A). Methods A total of 60 male KM mice were divided into six groups randomly, including control group, Con A model group, bifendate (BIF) group and three BA groups with gradient concentrations. Saline diluted BA (30 mg·kg-1, 15 mg·kg-1, 7.5 mg·kg-1) was given orally to mice. After 15 days' BA pretreatment, mice were then injected with Con A (20 mg·kg-1) to establish the mouse model with acute immune liver injury. Automatic biochemical analyzer was conducted to determine serum liver function indices such as plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST);ELISA was used to determine the levels of serum inflammatory cytokines (IL-2, IL-4, IL-10, TNF-α, IFN-γ); Western blot was used to detect the expression of liver tissue apoptosis related proteins (Bcl-2 and activated-Caspase-3). Results Compared with the control group, Con A treated mice showed significantly lower serum ALT and AST levels, while the levels of inflammatory cytokines (IL-2, IL-4, IL-10, TNF-α, IFN-γ) increased significantly. The expression of Bcl-2 was significantly decreased (P<0.05), whereas the expression of activated-Caspase-3 was significantly increased (P<0.01). Compared with the Con A model group, the mice that treated with different doses of BA, especially the middle and high dose groups, showed significantly reduced serum ALT and AST levels, as well as significantly decreased serum IL-2, IL-4, TNF-α and IFN-γ levels but increased IL-10. The apoptosis related proteins Bcl-2 and activated-Caspase-3 also showed contrary expression changes: the former increased while the latter decreased. Conclusion These findings suggested that BA had antagonistic action on the mouse with acute immune liver injury induced by Con A to some extent, and the mechanism of this process may be related with the anti-apoptosis and anti-inflammatory functions of BA to reduce the toxic effects of T lymphocytes.
2016,35(4): 511-516 收稿日期:2016-04-18
DOI:10.11984/j.issn.1000-7083.20160091
分类号:Q78
基金项目:国家自然科学基金项目(31372225);中央民族大学学科建设项目(YLDX01013);社会医学学术团队建设项目(2015MDTD13C);高等学校学科创新引智计划(B08044)
作者简介:汪佰莉(1979-),E-mail:13811636247@163.com;吴焕童(1992-),E-mail:13810472177@163.com;曹畅(1991-),E-mail:caochang511@163.com
*通讯作者:张淑萍,E-mail:bjqinxiaoyan@muc.edu.cn;覃筱燕,E-mail:zhangshuping@muc.edu.cn
参考文献:
孙嘉, 马丹, 王萍, 等. 2015. 白桦脂酸联合硼替佐米诱导U266细胞凋亡及其机制研究[J]. 贵阳医学院学报, 40(10):1024-1028.
杨逸, 覃筱燕, 郭哲, 等. 2015. 人参皂苷Rg1对小鼠免疫性肝损伤保护作用[J]. 中国公共卫生, 31(3):309-311.
张琛琛, 鲁佩, 田玉科, 等. 2014. 白桦脂酸预处理对小鼠脑缺血再灌注时氧化应激反应的影响[J]. 中华麻醉学杂志, 34(7):859-862.
郑晨宏, 谢晓华. 2016. 刀豆蛋白A诱导肝损伤模型中免疫细胞及因子研究进展[J]. 解放军医学院学报, 37(2):191-194.
Chen J, Duan L, Xiong A, et al. 2012. Blockade of IL-33 ameliorates Con A-induced hepatic injury by reducing NKT cell activation and IFN-γ production in mice[J]. Journal of Molecular Medicine, 90(12):1505-1515.
Cichewicz RH, Kouzi SA. 2004. Chemistry biological activity and chemotherapeutic potential of Betulinic acid for the prevention and treatment of cancer and HIV infection[J]. Medicinal Research Reviews, 24(1):90-114.
Fullerton AM, Roth RA, Ganey PE. 2013. Pretreatment with TCDD exacerbates liver injury from Concanavalin A:critical role for NK cells[J]. Toxicollogical Sciences, 136(1):72-85.
Gantner F, Leist M, Lohse AW, et al. 1995. Concanavalin A-induced T cell-mediated hepatic injury in mice:the role of tumor mecrosis factor[J]. Hepatology, 21(1):190-198.
Gong Q, Zhang H, Li J, et al. 2010. High-mobility group box 1 exacerbates concanavalin A-induced hepatic injury in mice[J]. Journal of Molecular Medicine, 88(12):1289-1298.
Guilhot S, Miller T, Cornman G, et al. 1996. Apoptosis induced by tumor mecrosis factor-alpha in rat hepatocyte cell lines expressing hepatitis B virus[J]. The American Journal of Pathology, 148(3):801-814.
Kakumu S, Okurnra A, Ishikawa T, et al. 1997. Production of interleukin-10 and 12 by peripheral blood monoclear cells (PBMC) in chronic hepatitis C virus (HCV) infection[J]. Clinical & Experimental Immunology, 108(1):138-143.
Mizuhara H, Uno M, Seki N, et al. 1996. Critical involvement of interferon gamma in the pathogenesis of T-cell activation-associated hepatitis and regulatory mechanisms of interleukin-6 for the manifestations of hepatitis[J]. Hepatology, 23(6):1608-1615.
Muñoz-Pinedo C. 2012. Signaling pathways that regulate life and cell death:evolution of apoptosis in the context of self-defense[J]. Advances in Experimental Medicine and Biology, 738:124-143.
Qin XY, Li T, Yan L, et al. 2010. Tanshinone ⅡA protects against immune-mediated liver injury through activation of T-cell subsets and regulation of cytokines[J]. Immunopharmacology & Immunotoxicology, 32(1):51-55. Schühly W, Heilmann J, Calis I, et al. 1999. New triterpenoids with antibacterial activity from Zizyphus joazeiro[J]. Planta Medica, 65(8):740-743.
Tiegs G, Hentschel J, Wendel A. 1992. A T cell-denendent experimental liver injury in mice inducible by Concanavalin A[J]. The Journal of Clinical Investigation, 90(1):196-203.
Tsutsui H, Nishiguchi S. 2014. Importance of kupffer cells in the development of acute liver injuries in mice[J]. International Journal of Molecular Sciences, 15(5):7711-7730.
Wahl C, Wegenka UM, Leithäuser F, et al. 2009. IL-22-dependent attenuation of T cell-dependent (Con A) hepatitis in herpes virus entry mediator deficiency[J]. The Journal of Immunology, 182(8):4521-4528.
Wang C, Nie H, Li K, et al. 2012. Curcumin inhibits HMGB1 releasing and attenuates concanavalin A-induced hepatitis in mice[J]. European Journal of Pharmacology, 697(1):152-157.
Yang XP, Liu TY, Qin XY, et al. 2014. Potential protection of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside against staurosporine-induced toxicity on cultured rat hippocampus neurons[J]. Neuroscience Letters, 576(2):79-83.
Zhang XL, Quan QZ, Sun ZQ, et al. 2001. Protective effects of cyclosporine A on T-cell dependent Con A-induced liver injury in Kunming mice[J]. World Journal of Gastroenterol, 7(4):569-571.
Zhou YQ, Dai WQ, Lin CL, et al. 2013. Protective effects of necrostatin-1 against concanavalin A-induced acute hepatic injury in mice[J]. Mediators of Inflammation, (2013):706156.
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