地塞米松联合川芎嗪对肺纤维化大鼠肺泡灌洗液中肿瘤坏死因子-α和转化生长因子-β1含量及肺纤维化程度的影响

Objective To explore the effects of dexamethasone combined with ligustrazine on the content of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta 1 (TGF-β1) in bronchoalveolar lavage fluid (BALF) from pulmonary fibrosis induced by bleomycin (BLM) in rats and the degree of pulmonary fibrosis. Methods Sixty male SD rats were randomly divided into 5 groups: normal control group (N group, n=12), pulmonary fibrosis model group (M group, n=12), dexamethasone intervention group (D group, n=12), ligustrazine intervention group (L group, n=12) and dexamethasone combined with ligustrazine intervention group (DL group, n=12). The rats in M, D, L and DL group were treated with BLM 5 mL/kg (dissolved in 0.9% sodium chloride solution 0.3 mL) by intratracheal instillation to induce pulmonary fibrosis, and the rats in N group with 0.9% sodium chloride solution 0.3 mL instead. Then the rats were given intraperitoneal injection of 0.9% sodium chloride solution 2 mL for N and M group, dexamethasone 3 mg/kg (dissolved in 0.9% sodium chloride solution 2 mL) for D group, ligustrazine 50 mg/kg (dissolved in 0.9% sodium chloride solution 2 mL) for L group, dexamethasone 3 mg/kg combined with ligustrazine 50 mg/kg (dissolved in 0.9% sodium chloride solution 2 mL) for DL group everyday.All of rats were killed at the 28th day.The content of TNF-α and TGF-β1 in BALF were measured by enzyme-linked immunosorbent assay (ELISA), and the histopathology of pulmonary fibrosis was observed by light microscope. Results The content of TNF-α and TGF-β1 in BALF of D group, L group and DL group were lower than that of M group, and the difference was statistically significant (all P<0.05). The content of TNF-α and TGF-β1 of DL group were (25.182±4.823) pg/mL, (14.047±2.234) pg/mL respectively, and lower than that of D group and L group, the difference was statistically significant (all P<0.05). The results of histopathology showed the structure of alveoli of N group was normal, whereas no normal alveolar structure and massive infiltrated fibroblast could be observed in M group. Compared with M group, the severity of pulmonary fibrosis of D group and L group reduced, and thickening alveoli septum and compressed and distorted alveoli could be observed. Compared with D group and L group, the severity of fibrosis of DL group reduced further, and alveoli structure could be observed in some districts. The semiquantitative score of pulmonary fibrosis of M group, D group, L group and DL group were 6 (5.00, 6.75), 5 (4.00, 5.75), 5(4.25, 5.75) and 4 (4.00, 5.00) respectively. The score of D group, L group and DL group were less than that of M group, and the difference was statistically significant (all P<0.05). The score of DL group was less than that of D group and L group , and the difference was statistically significant (all P<0.05). Conclusion Dexamethasone combined with ligustrazine can reduce the content of TNF-α and TGF-β1 in BALF and decrease the severity of pulmonary fibrosis in rats than one single drug, which contribute to combination therapy for pulmonary fibrosis. Key words: Dexamethasone; Pulmonary fibrosis; Tumor necrosis factor-alpha; Transforming growth factor-beta 1; Ligustrazine