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Journal of Chinese Integrative Medicine ›› 2008, Vol. 6 ›› Issue (9): 946-951.doi: 10.3736/jcim20080914

• Original Experimental Research • Previous Articles     Next Articles

Activator protein-1 mRNA expression, cell proliferation and collagen synthesis induced by tumor necrosis factor-α in cardiac fibroblasts from rats and the effect of Qiangxin Decoction

Yan Shen1, Shi-yun Yan2()   

  1. 1. Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China
    2. Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Received:2008-01-16 Online:2008-09-20 Published:2008-09-15

Objective: To investigate the function of activator protein-1 (AP-1) in proliferation and collagen synthesis of cardiac fibroblasts (CFs) in neonatal rats induced by tumor necrosis factor-α (TNF-α), and to explore the mechanism of Qiangxin Decoction (QXD), a compound traditional Chinese herbal medicine, in reversing cardiac fibrosis.
Methods: CFs derived from neonatal rats were cultured with enzymatic dissociation, and fibrosis of the CFs was induced by TNF-α. The CFs were divided into normal control group, untreated group, 5% QXD-containing serum group, 10% QXD-containing serum group and 20% QXD-containing serum group. After 24-hour culture of QXD-containing serum, AP-1 mRNA was detected by real-time fluorescent quantitative polymerase chain reaction; proliferation and collagen synthesis of CFs were assayed by thiazolyl blue assay (MTT) and measured by hydroxyproline respectively, in order to determine the effect of different dosage decoction on the proliferation and collagen synthesis of CFs.
Results: After 24-hour stimulation of TNF-α in CFs, compared with those in normal control group, the expression of AP-1 mRNA and cardiac fibroblast proliferation and collagen synthesis increased significantly (P<0.05). However, Qiangxin Decoction could reduce the expression of AP-1 mRNA and decreased the proliferation and collagen synthesis of CFs significantly (P<0.05).
Conclusion: Qiangxin Decoction can inhibit proliferation and collagen synthesis of CFs induced by TNF-α, and reverse cardiac fibrosis, which may be related to its down-regulation of the expression of AP-1.

Key words: cardiac fibrosis, cardiac remodeling, tumor necrosis factor-a, activator protein-1, Qiangxin Decoction, rats

CLC Number: 

  • R289.5

Table 1

Effect of Qiangxin Decoction-containing serum on proliferation of CFs(x±s)"

Group n A value
Normal control 8 0.618±0.187
Untreated 8 0.925±0.249*
5% QXD-containing serum 8 0.661±0.118
10% QXD-containing serum 8 0.645±0.189
20% QXD-containing serum 8 0.723±0.278

Table 2

Effect of Qiangxin Decoction-containing serum on hydroxyproline in cultured CFs(x±s, μg/ml)"

Group n Hydroxyproline content
Normal control 6 1.105±0.528
Untreated 6 1.975±0.873*
5% QXD-containing serum 6 1.724±0.759
10% QXD-containing serum 6 1.138±0.779
20% QXD-containing serum 6 1.992±0.976

Table 3

Effect of Qiangxin Decoction-containing serum on AP-1 expression in cultured CFs(x±s,×103 copy)"

Group n AP-1 mRNA
Normal control 4 2.792±0.146
Untreated 4 17.399±1.498*
5% QXD-containing serum 4 12.308±2.170
10% QXD-containing serum 4 9.552±0.855
20% QXD-containing serum 4 15.256±2.910
[1] Dai GZ, Gu FS, Qi WH , et al. Treatment recommendation on chronic systolic heart failure[J]. Zhonghua Xin Xue Guan Bing Za Zhi, 2002,30(1):7-23
doi: 10.3969/j.issn.1671-8801.2014.03.190
戴闺柱, 顾复生, 戚文航 . 慢性收缩性心力衰竭治疗建议[J]. 中华心血管病杂志, 2002,30(1):7-23
doi: 10.3969/j.issn.1671-8801.2014.03.190
[2] Jiang XC, Jiang XL, Li SQ . Current research on the pathogenesis, treatment and prevention of myocardial fibrosis[J]., 2006,12(15):931-933
doi: 10.3969/j.issn.1006-2084.2006.15.017
姜秀春, 姜秀丽, 李树青 . 心肌纤维化发病机制和防治的研究进展[J]. 医学综述, 2006,12(15):931-933
doi: 10.3969/j.issn.1006-2084.2006.15.017
[3] Burlew BS, Weber KT . Connective tissue and the heart. Functional significance and regulatory mechanisms[J]. Cardiol Clin, 2006,18(3):435-442
[4] Zhou SP, Yang CM . Inflammation and heart failure[J]. Xin Xue Guan Bing Xue Jin Zhan, 2007,28(3):493-496
周素平, 杨成明 . 炎症和心力衰竭[J]. 心血管病学进展, 2007,28(3):493-496
[5] Bond M, Chase AJ, Baker AH , et al. Inhibition of transcription factor NF-kappaB reduces matrix metalloproteinase-1, -3 and -9 production by vascular smooth muscle cells[J]. Cardiovasc Res, 2001,50(3):556-565
doi: 10.1016/S0008-6363(01)00220-6
[6] Diwan A, Dibbs Z, Nemoto S , et al. Targeted overexpression of noncleavable and secreted forms of tumor necrosis factor provokes disparate cardiac phenotypes[J]. Circulation, 2004,109(2):262-268
doi: 10.1161/01.CIR.0000109642.27985.FA
[7] Li YK. Experimental methodology of traditional Chinese medicine pharmacology[M]. Shanghai: Shanghai Scientific and Technical Publishers,2006: 50
李仪奎 . 中药药理实验方法学[M]. 上海: 上海科学技术出版社,2006: 50
[8] Li C. Fundamentals and clinic of organ fibrosis[M]. Beijing: People's Medical Publishing House,2003: 258-261
李才 . 器官纤维化基础与临床[M]. 北京: 人民卫生出版社,2003: 258-261
[9] Weber KT, Brilla CG, Janicki JS . Myocardial fibrosis: functional significance and regulatory factors[J]. Cardiovasc Res, 1993,27(3):341-348
doi: 10.1093/cvr/27.3.341 pmid: 8490934
[10] Swynghedauw B . Molecular mechanisms of myocardial remodeling[J]. Physiol Rev, 1999,79(1):215-262
doi: 10.1152/physrev.1999.79.1.215
[11] Niu XG, Zhao YL . The mechanism and therapeutics of myocardial remodeling secondary to chronic heart failure[J]. Xin Xue Guan Bing Xue Jin Zhan, 2005,26(3):281-284
doi: 10.3969/j.issn.1004-3934.2005.03.019
牛杏果, 赵玉兰 . 慢性心力衰竭心肌重塑机制及干预治疗[J]. 心血管病学进展, 2005,26(3):281-284
doi: 10.3969/j.issn.1004-3934.2005.03.019
[12] Pasic J, Levy WC, Sullivan MD . Cytokines in depression and heart failure[J]. Psychosom Med, 2003,65(2):181-193
doi: 10.1097/01.PSY.0000058372.50240.38 pmid: 12651985
[13] Bi Y, Luo M . Proto-oncogene and heart failure[J]. Guo Wai Yi Xue Xin Xue Guan Ji Bing Fen Ce, 2005,32(1):39-41
doi: 10.3969/j.issn.1673-6583.2005.01.016
毕莹, 罗明 . 原癌基因与心力衰竭[J]. 国外医学心血管疾病分册, 2005,32(1):39-41
doi: 10.3969/j.issn.1673-6583.2005.01.016
[14] Liu H, Yao YM . Advances in cross-talk of cellular signalling pathways associated with inflammatory response[J]. Zhongguo Bing Li Sheng Li Za Zhi, 2005,21(8):1607-1613, 1627
刘辉, 姚咏明 . 细胞内炎症信号通路交汇作用研究进展[J]. 中国病理生理杂志, 2005,21(8):1607-1613, 1627
[15] Huang CY, Zhu JH . Role of mitogen-activated protein kinase in myocardial hypertrophy[J]. Zhongguo Bing Li Sheng Li Za Zhi, 2005,21(7):1435-1439
doi: 1000-4718
黄朝阳, 朱建华 . 丝裂原活化蛋白激酶信号途径在心肌肥厚中的作用进展[J]. 中国病理生理杂志, 2005,21(7):1435-1439
doi: 1000-4718
[16] Zheng M, Wu JL . C-fos gene and cardiovascular diseases[J]. Xin Xue Guan Bing Xue Jin Zhan, 2002,23(5):310-312
doi: 10.3969/j.issn.1004-3934.2002.05.018
郑敏, 吴基良 . c-fos与心血管疾病[J]. 心血管病学进展, 2002,23(5):310-312
doi: 10.3969/j.issn.1004-3934.2002.05.018
[17] Zhang JL, Cui ZQ . Study on experimental method of traditional Chinese herbal medicine serum pharmacology[J]. Zhong Yi Yao Xue Kan, 2004,22(12):2271-2272
doi: 10.3969/j.issn.1673-7717.2004.12.055
张金梁, 崔志清 . 中药血清药理学实验方法的研究探微[J]. 中医药学刊, 2004,22(12):2271-2272
doi: 10.3969/j.issn.1673-7717.2004.12.055
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