鸢尾黄素对肝星状细胞外基质表达的影响

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (2): 175-180.

鸢尾黄素对肝星状细胞外基质表达的影响

王志勇¹, 吴俊华², 王玉蓉², 余德才¹, 丁义涛¹

¹南京大学医学院附属鼓楼医院肝胆研究所,南京 210008,江苏;
²南京大学医学院,南京 210008,江苏

收稿日期:2011-10-27 修回日期:2011-12-27 出版日期:2012-02-26 发布日期:2012-03-12
通讯作者: 丁义涛,男,主任医师,博士生导师,研究方向:生物人工肝、肝癌的治疗。Tel: 025-83304616 E-mail: drdingyitao@sina.com
作者简介:王志勇,男,硕士研究生,研究方向:肝硬化、肝癌的生物治疗。E-mail: nqsba@hotmail.com

Effects of tectorigenin on the secretion of extracellular matrix in Hepatic stellate cells

WANG Zhi-yong¹, WU Jun-hua², WANG Yu-rong², YU De-cai¹, DING Yi-tao¹

¹Hepatobiliary Surgery Research Institute, the Affiliated Drum Tower Hospital of Nanjing University, Nanjing 210008, Jiangsu, China;
²Medical School of Nanjing University, Nanjing 210008, Jiangsu, China

Received:2011-10-27 Revised:2011-12-27 Online:2012-02-26 Published:2012-03-12

摘要/Abstract

摘要： 目的: 研究鸢尾黄素对肝星状细胞的活化以及细胞外基质合成和降解的影响。方法: 体外培养大鼠肝星状细胞株HSC-T6,通过荧光定量PCR法检测鸢尾黄素对肝星状细胞的Ⅰ型胶原、α-肌动球蛋白(α-SMA)、基质金属蛋白酶-13(MMP-13)以及基质金属蛋白酶-1抑制剂(TIMP-1)mRNA的表达的影响。结果: 鸢尾黄素能显著抑制肝星状细胞中Ⅰ型胶原及活化标志α-SMA mRNA的表达,增强肝星状细胞中MMP-13 mRNA的表达,降低TIMP-1 mRNA的表达。结论: 鸢尾黄素既可以有效地抑制肝星状细胞的活化,同时又能减少肝星状细胞胞外基质的合成以及增加胞外基质的降解,因而具有潜在的抗肝纤维化的作用。

关键词: 鸢尾黄素, 肝纤维化, 肝星状细胞, 胞外基质

Abstract: To investigate the effect of tectorigenin on the secretion of extracellular matrix (ECM) in Hepatic stellate cells.METHODS: HSC-T6 cells were incubated with tectorigenin at different concentrations, the mRNA expression of α-SMA, pro-collagen-α₁(Ⅰ), MMP-13 and TIMP-1 were detected by real-time PCR.RESULTS: Tectorigenin significantly decreased the expression of α-SMA in HSC-T6, as well as the mRNA expression of pro-collagen-α₁, and tectorigenin significantly elevated the mRNA expression of MMP-13, while decreasing the mRNA expression of TIMP-1.CONCLUSION: Tectorigenin could reduce the synthesis and secretion of type Ⅰ collagen in HSC, thereby reducing the deposition of extracellular matrix; the other hand, tectorigenin could promote the degradation of extracellular matrix, so as to have anti-fibrosis potentials.

Key words: Tectorigenin, Liver fibrosis, Hepatic stellate cells, Extracellular matrix

中图分类号:

R965.2

王志勇, 吴俊华, 王玉蓉, 余德才, 丁义涛. 鸢尾黄素对肝星状细胞外基质表达的影响[J]. 中国临床药理学与治疗学, 2012, 17(2): 175-180.

WANG Zhi-yong, WU Jun-hua, WANG Yu-rong, YU De-cai, DING Yi-tao. Effects of tectorigenin on the secretion of extracellular matrix in Hepatic stellate cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(2): 175-180.

参考文献

[1] de Villiers WJ, Song Z, Nasser MS, et al. 4-Hydroxynonenal-induced apoptosis in rat hepatic stellate cells: Mechanistic approach[J]. J Gastroenterol Hepatol,2007, 22(3): 414-422.
[2] Chong LW, Hsu YC, Chiu YT, et al. Anti-fibrotic effects of thalidomide on hepatic stellate cells and dimethylnitrosamine-intoxicated rats[J]. J Biomed Sci, 2006,13 (3): 403-418.
[3] Kang KA, Lee KH, Chae S, et al. Cytoprotective effect of tectorigenin, a metabolite formed by transformation of tectoridin by intestinal microflora, on oxidative stress induced by hydrogen peroxide[J]. Eur J Pharmacol,2005,519 (1/2): 16-23.
[4] Lee HU, Bae EA, Kim DH. Hepatoprotective effect of tectoridin and tectorigenin on tert-butyl hyperoxide-induced liver injury[J]. J Pharmacol Sci, 2005,97(4): 541-544.
[5] Fang R, Houghton PJ, Hylands PJ. Cytotoxic effects of compounds from Iris tectorum on human cancer cell lines[J]. J Ethnopharmacol,2008,118(2):257-263.
[6] Jung SH, Lee YS, Lim SS, et al. Antioxidant activities of isoflavones from the rhizomes of Belamcanda chinensis on carbon tetrachloride-induced hepatic injury in rats[J]. Arch Pharm Res, 2004, 27(2):184-188.
[7] Lee HU, Bae EA, Kim DY. Hepatoprotective effect of tectoridin and tectorigenin on tert-butyl hyperoxide-induced liver injury[J]. J Pharmacol Sci, 2005, 97(4):541-544.
[8] Wu JH, Wang YR, Huang WY, et al. Anti-proliferative and pro-apoptotic effects of tectorigenin on hepatic stellate cells[J]. World J Gastroenterol, 2010,16 (31): 3911-3918.
[9] 孙建光. 补肾化瘀方对肝纤维化大鼠肝组织MMP-1/TIMP-1活性的影响[J]. 山东中医杂志, 2009, 28(1):52-54.
[10] 戴永美,蔡立勉,林棱. 奥曲肽对肝星状细胞胶原合成及TIMP-1/MMP-2表达的影响[J].临床肝胆病杂志,2008,24(5):332-334.
[11] 赵春洪,张晓岚. MMPs在肝纤维化形成与逆转过程中的作用[J]. 临床肝胆病杂志,2009,25(3):231-235.
[12] 李紫琼,郑勇. TIMPs和MMPs与肝纤维化研究进展[J].实用肝脏病杂志,2007,10(5):355-357.
[13] 白艳锋,尤红. 肝纤维化形成中MMPs/TIMPs的动态变化及治疗进展[J]. 肝脏,2009,14(2):162-163.
[14] 吴俊华,陈运喜,周添,等. 鸢尾黄素的制备及其对化学诱导的大鼠肝纤维化的保护作用[J]. 药学学报,2007,42:33-37.
[15] Hemmann S, Graf J, Roderfeld M, et al. Expression of MMPs and TIMPs in liver fibrosis-a systematic review with special emphasis on anti-fibrotic stragies[J]. J Hepatol,2007,46 (5):955-975.
[16] Wu LM, Wu XX, Sun Y,et al. A novel synthetic oleanolic acid derivative (CPU-II2) attenuates liver fibrosis in mice through regulating the function of hepatic stellate cells[J]. J Biomed Sci,2008,15 (2): 251-259.
[17] Mann DA, Smart DE. Transcriptional regulation of hepatic stellate cell activation[J]. Gut,2002,50 (6):891-896.
[18] Roderfeld M, Hemmann S, Roeb E. Mechanisms of fibrolysis in chronic liver injury[J]. Z Gastroenterol,2007,45 (1):25-33.
[19] Okazaki I, Arai M, Wada N, et al. Gene expression of MMPs and TIMPs in the procrss of hepatic fibrosis[J]. Nippon Rinsho,1993,51(2):428-434.
[20] Arthur MJ, Mann DA, Iredale JP. Tissue inhibitors of metalloproteinases, hepatic stellate cells and liver fibrosis[J]. J Gastroenterol Hepatol,1998,13 Suppl:S33-38.