[Effect of Chinese herbal drugs and tetrandrine on TGF-beta1 signaling pathway].
OBJECTIVE
To investigate the molecule mechanism of the anti-fibrotic effects of Chinese herbal drugs (Qidan granules) in rats.


METHODS
The male rats were randomly divided into four experimental groups: normal group, model group, Qidan group, tetrandrine group. Every group had 10 rats. Normal group were treated with physiologic saline while others were treated with silicon dioxide (50 mg/rat) by intratracheal instillation to induce silicosis. On 30th day Qidan group and Tetrandrine group were treated with Qidan granules (3125 mg/kg) or treated with tetrandrine (22 mg/kg) respectively. All the rats were scarified after 5 months. Lung/body coefficient was measured. Content of hydroxyproline was measured by alkaline hydrolysis. The gene expression of transforming growth factor-beta1 in bronchoalveolar lavage fluid was examined by using enzyme-linked immunosorbent assay (ELISA). The gene expressions of transforming growth factor-beta1, transcription factor Smad 3 and Smad 7 in lung were analyzed by using immunohistochemical technique (SP) and the image analysis.


RESULTS
Model group mainly had Grade III approximately IV silicotic nodule while Qidan group and tetrandrine group had Grade II silicotic nodule. In Qidan group and tetrandrine group, lung/body coefficient and content of hydroxyproline and expression of transforming growth factor-beta1 and Smad3 in lung and expression of transforming growth factor-beta1 in bronchoalveolar lavage fluid were lower than those in model group (P < 0.05). Expression of Smad 7 in lung was higher than model group (P < 0.05). Injury of kidney occurred in tetrandrine group.


CONCLUSIONS
Qidan granules and tetrandrine could inhibit expression of both Smad 7 and transforming growth factor-beta1 and promote expression of Smad 3. Qidan granules and tetrandrine could inhibit remarkably silicotic fibrosis in rats. Qidan granules are safer than tetrandrine.
Zhang
Hua-nan
HN
Shandong University Shandong Province Hospital, Jinan 250021, China.
Xin
Hong-tao
HT
Zhang
Wei-dong
WD
Xu
Shao-hua
SH
Zhang
Yan
Y
Jia
Qing
Q
D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D012829:Silicosis / Q000188:drug therapy / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D051906:Smad7 Protein; C497808:Smad7 protein, rat; D053773:Transforming Growth Factor beta1; C009438:tetrandrine