[Garlicin ameliorated pressure overload induced myocardial fibrosis in rats through partial inhibiting TGF-beta1 mediated Smads signal].
OBJECTIVE
To observe whether garlicin could ameliorate pressure overload induced myocardial fibrosis in rats through partial inhibiting transforming growth factor beta1 (TGF-beta1) mediated Smads signal.


METHODS
Forty male SD rats were randomly divided into 4 groups, i. e., the sham-operation group, the model group, the garlicin group, and the Tetramethylpyrazine (TMP) group, 10 in each group. The pressure overload induced myocardial fibrosis rat model was prepared using coarctation of aorta. Three days after modeling 5.0 mg/kg garlicin injection was administered to rats in the garlicin group, 20 mg/kg TMP injection to rats in the TMP group by peritoneal injection, while normal saline was peritoneally injected to rats in the sham-operation group and the model group. Four weeks after medication, the changes of myocardial collagen were observed by picrosirius red staining. The myocardial collagen volume fraction (CVF) and perivascular collagen areas (PVCA) were calculated. The serum transforming growth factor beta1 (TGF-beta1) expression was detected using ELISA. The TGF-beta1 protein expression in the myocardial tissue was observed using immunohistochemical assay. The changes of myocardial Smad2 and Smad7 mRNA expressions were detected using Real-time RT-PCR. The effects of garlicin on TGF-beta1 mediated Smad Signaling through luciferase assay were further verified using Mv1 Lu-(CAGA) 12-Luc cell line response to TGF-beta1.


RESULTS
Compared with the sham-operation group, the myocardial levels of CVF and PVCA, the serum TGF-beta1 level, and the TGF-beta1 protein expression in the myocardial tissue obviously increased in the model group (P < 0.05, P < 0.01). Compared with the model group, the PVCA level, the serum TGF-beta1 level, and the TGF-beta1 protein expression in the myocardial tissue of the garlicin group and the TMP group obviously decreased (P < 0.05, P 0O 01). The Smad2 mRNA expression was up-regulated while Smad7 mRNA expression down-regulated in the model group. The Smad2 mRNA expression was obviously down-regulated in the garlicin group and the TMP group (P < 0.05). The Smad7 mRNA expression was obviously up-regulated in the TMP group (P > 0.05). One to 2 microg/mL garlicin could obviously inhibit the luciferase activities of corresponding TGF-beta1, under the stimulation of 2 ng/mL TGF-beta1 (P < 0.05).


CONCLUSIONS
Garlicin ameliorated pressure overload induced myocardial fibrosis in rats through partial inhibiting TGF-beta-Smads signal pathway.
National Integrative Medicine Center for Cardiovascular Diseases, China-Japan Friendship Hospital, Ministry of Health, Beijing 100029.
Hai-Xiao
HX
Zhang
Zai-Xiang
ZX
Shi
Hai-Zhong
HZ
Jia
D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004220:Disulfides / Q000494:pharmacology*; D005355:Fibrosis; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000498:Allyl Compounds; D004220:Disulfides; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; C028009:diallyl disulfide