[Activator protein-1 mRNA expression, cell proliferation and collagen synthesis induced by tumor necrosis factor-alpha in cardiac fibroblasts from rats and the effect of Qiangxin Decoction].
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-alpha (TNF-alpha), 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-alpha. 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-alpha 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).


CONCLUSIONS
Qiangxin Decoction can inhibit proliferation and collagen synthesis of CFs induced by TNF-alpha, and reverse cardiac fibrosis, which may be related to its down-regulation of the expression of AP-1.
Shen
Yan
Y
Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
Yan
Shi-Yun
SY
D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C530394:qiangxin; D003094:Collagen