Protective effect of hydroxysafflor yellow A on bleomycin- induced pulmonary inflammation and fibrosis in rats

To observe the effect of hydroxysafflor yellow A (HSYA), an active ingredient of a traditional Chinese herbal medicine Carthamus tinctorius L., on lung inflflammation and pulmonary fibrosis induced by bleomycin (BLM) in rats. 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 mgaEuro cent kg(-1)aEuro cent day(-1)) 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)-alpha, interleukin (IL)-1 beta, IL-6 and some cytokines in lung tissue were detected by real-time polymerase chain reaction. Nuclear factor-kappa B p65 or alpha-smooth muscle actin (alpha-SMA) protein distribution in rat lung tissue was observed by immunohistochemistry. On the 7th 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 (PaO2) increased (HSYA 80.0 mgaEuro cent kg(-1), P < 0.01) and CO2 partial pressure (PaCO2) decreased (HSYA 53.3, 80.0 mgaEuro cent kg(-1), P < 0.05). Moreover, the mRNA expression of TNF-alpha, IL-1 beta, and IL-6; and the number of NF-kappa B p65 positive cells was lower in HSYA 53.3 and 80.0 mgaEuro cent kg(-1) groups than those in the model group (all P < 0.05). Twenty-one days after BLM administration, HSYA or DXM treatment ameliorated fibrosis, increased PaO2 (HSYA 53.3, 80.0 mgaEuro cent kg-1, P < 0.01), and decreased PaCO2 (53.3 and 80.0 mgaEuro cent kg-1, P < 0.05). Further, the mRNA expression of TGF-beta 1, alpha-SMA, and collagen I as well as the number of alpha-SMA positive cells increased in the model group and HSYA can attenuate these changes (53.3, 80.0 mgaEuro cent kg(-1), 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 mgaEuro cent kg(-1), P < 0.05). HSYA could alleviate acute lung inflflammation and chronic pulmonary fibrosis induced by BLM in rats.