| Objective To observe the effects of resveratrol (RES) on the hydroxyproline (HYP) contents, the TGF beta1and ERK1/2expression in lung tissues of rats with bleomycin (BLM)-induced pulmonary fibrosis, and to explore the inhibitory role of RES in BLM-induced pulmonary fibrosis.Methods Sixty male SD rats were randomly divided into control group, model group, low dose RES intervention group (50mg/kg) and high dose RES intervention group (100mg/kg), and the model of pulmonary fibrosis was made by intratracheal instillation of BLM. RES was given to rats on the day14, and part rats in various groups were sacrificed on days17,24and31, respectively. MASSON stain, hydroxyproline (HYP) contents, and the expression levels of TGF beta1and ERK1/2mRNA and protein were determined in the pulmonary tissues.Result1The Masson stain in the lung tissues of rats By intratracheal injection of bleomycin after on the14day, the control group in the lung tissue of rats with bronchial wall collagen fiber was thin, alveolar wall spaced a small amount of collagen fibers deposition; alveolar septa fibroblasts increased significantly in the lung tissue of model group, fibrous tissue increased, the alveolar structure was damaged and collapsed. The rat tissues of the model group and RES low dose group with the17day, the24day, the31day have massive pulmonary interstitial collagen fiber flake and fascicular distribution, or even part of alveolar cavity by collagen fiber filled. The inflammation and pulmonary fibrosis reduced gradually in the high dose of RES group2Changes of HYP content In model group at each time point in the lung tissue of hydroxyproline contents increased significantly compared with those of the control group (P<0.05), and with the time increasing. RES low dose group and high dose of RES group HYP contents increased significantly compared with the control group, the difference was statistically significant (P<0.05); but the RES low dose group, high dose of RES group and model group in HYP had no significant difference on day17. The RES low dose group and high dose of RES group in lung tissue of rats with hydroxyproline contents than those in the model group on day24and31was significantly decreased (P<0.05), the difference was statistically significant, high dose of RES group decreased more obviously,3The changes of TGF-β1mRNA content and protein expression in lung tissues TGF-β1in the lung tissue of the rats in the control group showed a weak expression; Model group at each time point of TGF-β1expression were higher than those in control group (P<0.05),and on the seventeenth day was at the maximum; on the day of twenty-fourth and thirty-one in The RES low dose group and high dose of RES group, TGF beta1expression than those in model group had reduced, the high dose of RES group decreased more obviously.4The changes of ERK1/2mRNA and protein expression in lung tissues ERK1/2in the lung tissue of the control group was weak expression compare with the model group (P<0.05). ERK1/2expression in the model group were higher than those in the control group at each time, and on the seventeenth day was at the maximum, ERK1/2expression decreased as the passed by; RES low dose group, at twenty-fourth day, thirty-one day, ERK1/2expression is lower than that of the model group and the high dose group; ERK1/2expression in RES high dose group in seventeenth day, twenty-fourth day, thirty-one day were lower than the model group,(P<0.05), and with the passage of time decreased.Conclusion1.TGF-β1and ERK1/2are significantly increased in the rat lung tissues of BLM-induced pulmonary fibrosis, suggesting that they may play important roles in the occurrence and development of pulmonary fibrosis.2.RES can inhibit collagen synthesis by the blockade of MAPK/ERK pathway via inhibiting TGF-β1expression, thereby reducing the fibroblast and decreasing the extracellular matrix (ECM). |
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