Protective Effect of Hydroxysafflor Yellow A on Bleomycin-Induced Pulmonary Inflammation and Fibrosis in Rats

Objective: To observe the effect of hydroxysafflor yellow A（HSYA）, an active ingredient of a traditional Chinese herbal medicine Carthamus tinctorius L., on lung inflammation and pulmonary fibrosis induced by bleomycin（BLM） in rats. Methods: Animals were divided into 6 groups including normal group, model group, three HSYA groups and dexamethasone（DXM） group. Three doses of HSYA(35.6, 53.3, and 80.0 mg·kg;·day;) were intraperitoneally（i.p.） injected in rats for 3 weeks after BLM administration and DXM was used as the positive control（n=8 or 12）. Arterial blood gas was assayed and morphological changes were observed. Lung mRNA expressions of tumor necrosis factor（TNF）-α, interleukin（IL）-1β, IL-6 and some cytokines in lung tissue were detected by real-time polymerase chain reaction. Nuclear factor-κB p65 or α-smooth muscle actin（α-SMA） protein distribution in rat lung tissue was observed by immunohistochemistry. Results: On the 7 th day after BLM administration, lung tissue showed serious inflammation. Treatment with HSYA or DXM ameliorated lung inflammation. After treatment with HSYA or DXM, oxygen partial pressure（PaO;） increased(HSYA 80.0 mg·kg;, P<0.01) and CO;partial pressure（PaCO;） decreased(HSYA 53.3, 80.0 mg·kg;, P<0.05). Moreover, the mRNA expression of TNF-α, IL-1β, and IL-6; and the number of NF-κB p65 positive cells was lower in HSYA 53.3 and 80.0 mg·kg;groups than those in the model group（all P<0.05）. Twenty-one days after BLM administration, HSYA or DXM treatment ameliorated fibrosis, increased PaO;(HSYA 53.3, 80.0 mg·kg;, P<0.01), and decreased PaCO;(53.3 and 80.0 mg·kg;, P<0.05). Further, the mRNA expression of TGF-β1, α-SMA, and collagen Ⅰ as well as the number of α-SMA positive cells increased in the model group and HSYA can attenuate these changes(53.3, 80.0 mg·kg;, P<0.05). Hematoxylin and eosin and Masson’s trichrome staining indicated that the fibrosis and collagen deposition were ameliorated in HSYA groups(53.3, 80.0 mg·kg;, P<0.05). Conclusion: HSYA could alleviate acute lung inflammation and chronic pulmonary fibrosis induced by BLM in rats.