microRNA let-7a在刀豆蛋白A诱导的小鼠肝损伤中的作用

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (7): 738-742.

microRNA let-7a在刀豆蛋白A诱导的小鼠肝损伤中的作用

汪向明¹, 吕坤², 张帆¹, 张莺莺³, 钟民², 李佳嘉¹, 梅晶晶¹

¹皖南医学院弋矶山医院病理科, 芜湖 241001,安徽;
²皖南医学院弋矶山医院中心实验室;
³检验科,芜湖 241001,安徽

收稿日期:2013-03-30 修回日期:2013-05-23 出版日期:2013-07-26 发布日期:2013-06-20
通讯作者: 吕坤,男,博士,副主任技师, 研究方向:感染免疫学。Tel: 0553-5739912 E-mail: lvkun315@126.com
作者简介:汪向明,男,硕士,主治医师,研究方向:免疫病理学。Tel: 0553-5739792 E-mail: bbbwcx666@163.com
基金资助:
安徽高校省级科学研究项目(KJ2012B204,KJ2011B198,KJ2011B191);安徽省自然科学基金项目(1308085QH137)

Effect of microRNA let-7a on Con A-induced hepatitis

WANG Xiang-ming¹, LV Kun², ZHANG Fan¹, ZHANG Ying-ying³, ZHONG Min², LI Jia-jia¹, MEI Jing-jing¹

¹Department of Pathology;
²Central Laboratory;
³Laboratory Medicine, Yijishan Hospital, Wannan Medical College, Wuhu 241001, Anhui, China

Received:2013-03-30 Revised:2013-05-23 Online:2013-07-26 Published:2013-06-20

摘要/Abstract

摘要： 目的: 探讨microRNA let-7a对刀豆蛋白A(Concanavalin A, ConA)小鼠肝损伤的保护作用。方法: 建立ConA诱导的小鼠肝损伤模型,采用尾静脉注射let-7a慢病毒表达质粒的方法,并在造模前 7 d 给予let-7a进行治疗干预。采用自动生化仪分析检测血清ALT变化;ELISA检测血清TNF-α、IL-6和干扰素-γ(IFN-γ)表达水平;HE染色肝脏组织病理学观察,评价let-7a治疗效果。结果: 治疗组血清ALT水平较模型组明显降低(P<0.01);与模型组相比,治疗组IL-6水平明显降低(P<0.01),治疗组血清炎症细胞因子TNF-α、IFN-γ水平也显著下降(P<0.05)。肝脏组织病理学检查显示,治疗组较模型组肝组织损伤程度明显减轻,炎症细胞明显减少(P<0.01, P<0.05)。治疗组小鼠生存率明显高于模型组(P<0.01)。结论: let-7a对ConA诱导的小鼠肝损伤有保护作用,该作用可能通过抑制相关炎症细胞因子TNF-α、IL-6和IFN-γ表达来实现。

关键词: microRNA, let-7a, 肝损伤

Abstract: AIM: To investigate the effects of microRNA let-7a on Con A-induced hepatitis.METHODS: 24 BALB/c mice were randomly divided into model group and let-7a treatment group. The liver hepatitis models were established by the tail vein injection of Con A. Mice was infected with a lentiviral vector containing the let-7a sequence 7 days before Con A treatment. The plasma alanine transaminase (ALT) activities were measured with a 7170 Hitachi automatic analyzer. The serum TNF-α, IL-6 and IFN-γ were determined with enzyme-linked immunosorbent assay (ELISA) kits. The liver samples were fixed in 10% formalin, embedded in paraffin, sectioned and then stained with hematoxylin and eosin for histological examinations.RESULTS: The serum ALT level was significantly decreased in the let-7a infected-mice compared to the control mice (P<0.001). Pretreatment with let-7a consistently reduced the extent of liver damage, as evidenced by the decreased infiltrated lymphocytes (P<0.05) and the limited number of necrotic lesions in these mice (P<0.01). Furthermore, let-7a significantly improved the survival rate after Con A treatment. It was accompanied by a significant decreased level of inflammatory cytokines as TNF-α, IL-6 and IFN-γ in the serum.CONCLUSION: MicroRNA let-7a ameliorates Con A-induced hepatitis. It may represent as a novel therapeutic strategy in treating immune-mediated inflammatory hepatitis.

Key words: MicroRNA, Let-7a, Hepatitis

中图分类号:

R965.2

汪向明, 吕坤, 张帆, 张莺莺, 钟民, 李佳嘉, 梅晶晶. microRNA let-7a在刀豆蛋白A诱导的小鼠肝损伤中的作用[J]. 中国临床药理学与治疗学, 2013, 18(7): 738-742.

WANG Xiang-ming, LV Kun, ZHANG Fan, ZHANG Ying-ying, ZHONG Min, LI Jia-jia, MEI Jing-jing. Effect of microRNA let-7a on Con A-induced hepatitis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(7): 738-742.

参考文献

[1] Tiegs G, Hentshel J, Wendel A. T cell-dependent experimental liver injury in mice induced by Concanavalin A[J]. J Clin Invest, 1992, 90(1): 196-203.
[2] Nakaya M, Hashimoto M, Nakagawa R, et al. SOCS3 in T and NKT cells negatively regulates cytokine production and ameliorates ConA induced hepatitis[J]. J Immunol, 2009, 183(11): 7047-7053.
[3] 李敏,金晓琨,李卫东.双氢青蒿素保护刀豆蛋白 A诱导的小鼠肝损伤及机制探讨[J].中国药理学通报, 2009, 25(5): 630-633.
[4] Meng F, Henson R, Hania WJ, et al. The MicroRNA let-7a modulates interleukin-6-dependent STAT-3 survival signaling in malignant human cholangiocytes[J]. J Biol Chem, 2007,282(11): 8256-8264.
[5] 张晓斐,于鹏丽,张红杰.microRNA和Th17细胞在炎症性肠病形成与发展中的作用[J].国际消化病杂志, 2012, 32(4): 226-229.
[6] Zhang Y, Wang X, Zhong M, et al. MicroRNA let-7a ameliorates con A-induced hepatitis by inhibiting IL-6-dependent Th17 cell differentiation[J]. J Clin Immunol, 2013, 33(3): 630-639.
[7] 王萍,尹桃,周伯庭. miRNA对骨质疏松症的调控[J]. 中国临床药理学与治疗学,2013, 18(1): 110-114.
[8] 龚志成,黄琼,刘昭前. miRNA在糖尿病中的研究进展[J].中国临床药理学与治疗学, 2010, 15(2): 214-218.
[9] 秦保东,仲人前,梁艳,等. microRNA在自身免疫性疾病中的研究进展[J].实用医院临床杂志,2012, 9(3): 21-25.
[10] Li QJ, Chau J, Ebert PJ, et al. miR-181a is an intrinsic modulator of T cell sensitivity and selection[J]. Cell, 2007, 129(1): 147-161.
[11] Lin YC, Kuo MW, Yu J, et al. c-Myb is an evolutionary conserved miR-150 target and miR-150/c-Myb interaction is important for embryonic development[J]. Mol Biol Evol, 2008, 25(10): 2189-2198.
[12] Xiao C, Calado DP, Galler G, et al. MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb[J]. Cell, 2007, 131(1): 146-159.
[13] Sch^TMmann J, Wolf D, Pahl A, et al. Importance of Kupffer cells for T-cell-dependent liver injury in mice[J]. Am J Pathol, 2000, 157(5): 1671-1683.

[1]	李士旭, 李林运, 王新, 李轲, 卞华. 银杏叶提取物通过miR-145/FOXO1轴对实验性肾功能衰竭大鼠肾脏损伤的影响[J]. 中国临床药理学与治疗学, 2023, 28(7): 728-735.
[2]	邢博民, 郭娜, 宁海慧, 丁新耘, 马玉清. Rho激酶抑制剂对脓毒症肝损伤的影响[J]. 中国临床药理学与治疗学, 2022, 27(5): 544-550.
[3]	刘文静, 武之涛, 潘国宇. 肝毒性风险的体外早期发现和预测[J]. 中国临床药理学与治疗学, 2021, 26(8): 923-930.
[4]	宋如铮, 彭英, 王广基, 孙建国. 定量蛋白质组学常用研究技术及其在肝源性疾病发病机制中的应用进展[J]. 中国临床药理学与治疗学, 2021, 26(5): 570-578.
[5]	高岩, 李均童, 吴青林, 李林, 张兰. 基于代谢组学研究二苯乙烯苷在对乙酰氨基酚诱导小鼠肝损伤中的保护作用[J]. 中国临床药理学与治疗学, 2021, 26(2): 161-166.
[6]	许丽娜, 李月, 彭金咏. microRNA与药物性肝损伤[J]. 中国临床药理学与治疗学, 2020, 25(7): 803-809.
[7]	王倩, 苏慧宗, 李玥, 谭波, 严东明, 金静怡, 裘福荣. 茵陈术附汤抑制TLR4/NF-κB通路对α-萘异硫氰酸酯诱导肝内胆汁淤积症模型小鼠肝损伤的保护作用[J]. 中国临床药理学与治疗学, 2020, 25(6): 601-609.
[8]	姜兵兵. microRNA在亨廷顿病中的研究进展[J]. 中国临床药理学与治疗学, 2020, 25(6): 677-685.
[9]	李红丽，文丹丹，贝承丽，高利臣，彭喜旭. 专项整治前后结核患者肝损伤及药物使用费用对比分析[J]. 中国临床药理学与治疗学, 2019, 24(9): 1030-1036.
[10]	朱林佳，原少斐，上官宗校，慈晓，赵仁国，李玉苹. microRNA-1304通过靶向血红素氧合酶-1对人肺癌细胞的抑制作用[J]. 中国临床药理学与治疗学, 2019, 24(4): 383-390.
[11]	何阳，宋立莹，彭向东，方伟进，王春江，邓珍珍，樊志强，刘世坤. 发酵虫草菌粉对DEN致大鼠肝损伤的保护作用及TGF-β1/Smads通路的影响[J]. 中国临床药理学与治疗学, 2018, 23(9): 974-982.
[12]	廖笑玲，吴亮，林宗泽，叶剑. 番茄红素抑制内质网应激从而减轻CCl₄诱导的小鼠急性肝损伤[J]. 中国临床药理学与治疗学, 2018, 23(7): 770-775.
[13]	郝少君，马俊杰，孔学军，苏峰，李军，李文俊，张正臣. 复方黄栌口服液对大鼠肝匀浆及肝组织的影响[J]. 中国临床药理学与治疗学, 2018, 23(6): 627-631.
[14]	徐明，崔鹏，叶敏，倪熊，王廷峰，闵志钧. miRNA-101在甲状腺髓样癌中抑癌机制的研究[J]. 中国临床药理学与治疗学, 2018, 23(5): 524-530.
[15]	钟正灵，张飞，江玉华，张炜婷，童九翠，李娟，储冀汝，谢海棠. 阿魏酸对急性肝损伤的保护作用[J]. 中国临床药理学与治疗学, 2018, 23(12): 1335-1339.