Objective: To explore the role of
transforming growth factor-β (TGF-β) signaling pathway in xiaotan huayu liqiao
traditional Chinese medicine compound (XC)'s anti-myocardial
fibrosis in chronic intermittent
hypoxia (CIH) rats. Methods: Forty SD rats were randomly divided into normoxia group,
oxygen +
traditional Chinese medicine compound group ( TCMC), Chronic intermittent
hypoxia model group (CIH), TCMC + CIH, 10 in each group. CIH cabin was built by filling with
nitrogen and
oxygen. Firstly, the volume fraction of
oxygen in the cabin reduced from 21% to 9% in 90 s by filling the cabin with
nitrogen. And then it gradually rose to 21% by reoxygenating in 90s, as a cycle. CIH and TCMC+CIH group rats were placed in the CIH device, while normoxia and TCMC group rats were placed in the normal
oxygen chamber. In addition, rats in TCMC +CIH group and TCMC group were treated with XC crude
drug (24 g/kg) daily by gavage, while rats in CIH group and normoxia group were given equal volume
normal saline. Using sirius red staining, the
collagen in myocardial interstitium was visualized. The
protein expressions of
collagen I,
collagen III and
fibronectin were detected by Western blot, p-Smad3, p-Smad2 and TGF-β
protein in the TGF-β/Smads signaling pathway were also analyzed by Western blot. The
mRNA expressions of
matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of
metalloproteinase -2(TIMP-2) were measured by real-time quantitative polymerase chain reaction (PCR). Results: Compared with the rats exposed to normoxia, the CIH rats showed obvious
collagen deposition,
protein expressions of
collagen I,
collagen III and
fibronectin were significantly increased in the myocardial tissue (P<0.01). The
protein expression levels of TGF-β, p-smad2 and p-smad3 in the myocardial tissue of the CIH rats were also significantly increased (P<0.01). The up-regulation of
TIMP-2 mRNA in the myocardial tissues resulted in the decrease of MMP-2
mRNA(P<0.01). XC reduced myocardial
fibrosis of CIH rats and inhibited the expressions of
collagen I and
collagen III and
fibronectin protein (P<0.05,P<0.01,P<0.05, respectively). The further mechanism study showed that XC inhibited the expression of TGF-β (P<0.01), which down-regulated the expressions of p-smad2, p-smad3 and
TIMP-2 (P<0.05). Conclusion: XC could reduce the expression of TGF-β and smad2/3 phosphorylation, down-regulate the expression of
TIMP-2, which would inhibit the formation of myocardial
fibrosis in CIH rats, and improve the myocardial function of CIH rats.