| Objective To investigate the role of arsenic trioxide in the mechanisms of lung fibrosis in rats and compare its effect and side effect with that of dexamethasone. Methods 110 Sprague-Dawley rats were randomly divided into seven groups including control group (group A), bleomycin group (group B), dexamethasone group (group C), arsenic trioxide group (group D), bleomycin plus dexamethasone group (group E), bleomycin plus arsenic trioxide group (group F), bleomycin plus low-dose dexamethasone plus low-dose arsenic trioxide group (group G). In Group A, C, and D, each had 10 rats and in other groups, each had 20 rats. Every group was divided into two subgroups, which were sacrificed respectively on day 7 or day 28. Bronchoalveolar lavage fluid (BALF) was obtained and the cell differentiation, inflammatory cell apoptosis as well as cytokines including interferon-gamma and transforming growth factor {3 , were detected. HE (Hematoxylin-eosin,HE) stain was performed on the lung tissue slices to observe the extent of alveolitis and fibrosis. The hydroxyproline assays of the lung tissues were also done on the day 28 rats to estimate the collagen content.Results 1. The weights of rats in group A, B, D and F increased during the observation, but the rats in group C, E and G had a weight loss in the first 7 days. On day 28, the average weights of rats in group A, B, D, F were significantly higher than that of other groups. 2. On day 7and day 28, the numbers of inflammatory cells in BALF of group C, E, G are higher than that of group A, B, D, F, among which, that of group B is the highest. 3.On day 7, the percentage of inflammatory cells in the BALF of group A is the lowest and the percentage of alveolar macrophages is the highest, while that of group B were on the contrary. There is statistical significance between group B and group E, or group F, or group G (PO.05). On day 28, the percentage of inflammatory cells in the BALF of rats with dexamethasone administration increased a lot, which may be related to infection. At same time, the percentage of inflammatory cells in the BALF of group B reduced, but still higher than those of group F (.PO.05). 4. Fewer cell apoptosis could be found in the BALF of group A, group B and group D on day 7 and 28. But it increased significantly in the BALF of group C, group E, group F and group G on day 7. On day 28, although the percentage of apoptosis in all groups declined, there were statistical significance between group F, group G and group B. 5. The level of interferon-gamma in BALF of group B was much higher than that of group E, group F and group G on day 7(P<0.05). 6. The level of transforming growth factor P i in BALF of group A and D was lower than that in other groups on day 7, while on day 28 the level of group B washigher than that of group F and group G (P<0.05). 7. The hydroxyproline content of group B was the highest but was not significantly different from that of group E and group F. The value of group G, however, was much more lower than that of group B, and there was statistical significance between them. 8. More severe inflammation was shown in the histological examination of the lung tissue slices of group B. However, in the lungs from group E, group F and group G, fibrotic lesions were observed, but their extent were limited and their intensity were attenuated compared with group B. Conclusion 1.Arsenic trioxide can ameliorate the formation of bleomycin-induced pulmonary fibrosis in rats, which might be related to its ability to induce inflammatory cells apoptosis and to reduce the concentrations of interferon-gamma in BALF. 2. Compared with dexamethasone arsenic trioxide is of more safe.
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