Effects Of Tea Polyphenols On Experimental Pulmonary Fibrosis And Its Mechanisms In Mice And Rats

Objective:To study the effects of tea polyphenols on bleomycin-induced pulmonary fibrosis in animals and explore its mechanisms.Methods:Mice were randomly divided into 6 groups : control group,model group, prednisolone group and high, moderate and low tea polyphenols groups. Rats were randomly divided into 5 groups : control group,model group,prednisolone group and high, low tea polyphenols groups. The experimental groups were injected intratracheally with bleomycin and were further treated with saline, tea polyphenols or prednisone, p.o. daily. The control group was received distilled water. The hydroxyproline (HYP) contents, glutathion (GSH) contents, total antioxidant capacity (T-Aoc) in lung tissue and lung index were assessed at the 7th, 14th or 28th day. Lung samples collected were sliced up, the changes of structure and ultrastructure were measured by the light microscope and the electron microscope. The expression of transforming growth factorβ1 (TGF-β1),α-smooth muscle actin (α-SMA) and collagen I (Col-I) were analyzed by immunohistochemistry; the expression of TGF-β1 andα-SMA mRNA were detected by semi-quantitative RT-PCR methods; the expression of TGF-β1,α-SMA, Col-I, collagen IV (Col-IV) and peroxisome proliferator-activated receptorγ(PPAR-γ) proteins were analyzed by western-blotting methods. Results:Tea polyphenols treatment obviously reduced lung index and lung HYP contents in mice and rats with pulmonary fibrosis, significantly improved the T-Aoc and GSH contents in lung tissue (P<0.01, P<0.05). The histological evaluation of lung specimens demonstrated that tea polyphenols dramatically decreased lung inflammation, lung fibrosis and improved the ultrastructure of pneumocytes (P<0.01, P<0.05). Tea polyphenols could significantly decrease the expression of protein TGF-β1,α-SMA and Col-I by immonohistostaing technique (P<0.01, P<0.05). Moreover, tea polyphenols could dramatically decreas the expression of TGF-β1 mRNA and protein,α-SMA mRNA and protein, Col-I protein and Col-IV protein (P<0.01, P<0.05), increase the expression of PPAR-γprotein (P<0.01, P<0.05).Conclusion:Tea polyphenols could alleviate bleomycin-induced pulmonary fibrosis in mice and rats, the mechanisms might be associated with the reinforcement of antioxidant systems and the up-regulation the protein expression of PPAR-γ, and the elevation of the mRNA and protein expression of TGF-β1 andα-SMA, which inhibited the proliferation of lung myofibroblast, and then regulation of the protein expression of Col-I and Col-IV to inhibit the over-express of extracellular martrix.