探讨地塞米松联合川芎嗪对博来霉素诱导肺纤维化大鼠肺泡灌洗液(BALF)中肿瘤坏死因子-α(TNF-α)和转化生长因子-β1(TGF-β1)含量及肺纤维化程度的影响。

将60只雄性SD大鼠随机分为5组，即正常对照组(N组)、模型组(M组)、地塞米松治疗组(D组)、川芎嗪治疗组(L组)和地塞米松联合川芎嗪治疗组(DL组)，N组大鼠气管内注入0.9%氯化钠溶液0.3 mL，其他4组大鼠气管内注入5 mg/kg博莱霉素(溶于0.3 mL 0.9%氯化钠溶液)进行肺纤维化造模，造模成功后N组、M组大鼠每天给予腹腔注射0.9%氯化钠溶液2 mL治疗，D组、L组和DL组大鼠分别每天给予腹腔注射地塞米松3 mg/kg(溶于2 mL 0.9%氯化钠溶液中)、川芎嗪50 mg/kg(溶于2 mL 0.9%氯化钠溶液中)和两种药物联合(地塞米松3 mg/kg、川芎嗪50 mg/kg溶于2 mL 0.9%氯化钠溶液中)治疗。各组大鼠在气管注入药物后第28天处死。用酶联免疫吸附试验(ELISA)检测各组大鼠BALF中TNF-α和TGF-β1的含量，用苏木精-伊红染色在光学显微镜下对大鼠肺组织病理标本进行观察并进行半定量评分。

与M组相比，D组、L组和DL组大鼠BALF中TNF-α、TGF-β1含量均下降，差异有统计学意义(均P<0.05)；与D组和L组相比，DL组大鼠BALF中TNF-α、TGF-β1含量(25.182±4.823)、(14.047±2.234)pg/mL均下降，差异有统计学意义(均P<0.05)。病理结果显示N组大鼠肺泡结构正常；M组大鼠肺泡结构消失，出现大量成纤维细胞；D组和L组大鼠可见肺泡间隔增宽，肺泡压缩变形，纤维化程度较M组减轻；DL组大鼠肺纤维化程度较D组和L组大鼠进一步减轻，部分区域可见肺泡结构。M组、D组、L组和DL组大鼠肺纤维化半定量评分分别为6(5.00，6.75)、5(4.00，5.75)、5(4.25，5.75)、4(4.00，5.00)分。与M组相比，D组、L组和DL组大鼠肺纤维化程度半定量评分均减少，差异有统计学意义(均P<0.05)。与D组和L组相比，DL组大鼠肺纤维化程度半定量评分减少，差异有统计学意义(均P<0.05)。

与单一药物相比，地塞米松联合川芎嗪治疗能更显著地降低大鼠BALF中TNF-α和TGF-β含量及减轻肺纤维化程度，两者联合应用可能适合肺纤维化治疗。

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.

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.

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).

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.