大黄素对肺纤维化大鼠的保护作用及部分机制研究

摘要

目的：观察大黄素对博莱霉素所致大鼠肺纤维化的影响,并探讨其保护机制。方法将60只♂ SD大鼠随机分为正常对照组、假手术组、模型组、大黄素低剂量干预组、大黄素高剂量干预组和泼尼松组,每组10只,后4组经气管内注入博莱霉素建立大鼠肺纤维化模型,从d2开始,低、高剂量干预组大鼠分别予20、80 mg · kg-1大黄素2 mL灌胃,泼尼松组以5 mg·kg-1醋酸泼尼松2 mL灌胃,其余2组予2 mL生理盐水灌胃,d 28处死所有大鼠,取出肺组织行HE染色和Masson 染色,测定肺组织羟脯氨酸( HYP )、丙二醛( MDA)、超氧化物歧化酶( SOD )、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)含量,采用酶联免疫吸附法(ELISA)测定血清肿瘤坏死因子-α(TNF-α)、白介素(IL)-6、IL-17浓度,通过Western blot分析肺组织中Kelch样ECH联合蛋白1( Keap 1)、NF-E2相关因子2( Nrf2)、核因子-κB ( NF-κB) p65表达。结果低、高剂量干预组及泼尼松组肺泡炎症和肺纤维化程度明显轻于模型组( P 0．05)。结论大黄素可能通过增强抗氧化能力及抑制炎症反应对肺纤维化大鼠产生保护作用。%Aim To observe the influence of emodin on bleomycin-induced pulmonary fibrosis in rats, and explore its protective mechanisms. Methods Sixty SD rats were randomly divided into normal control group, sham operation group, model group, low-dose inter-vention group, high-dose intervention group and pred-nisone group. Each group included 10 animals. Rats in the latter 4 groups were intratracheally administered with bleomycin to establish pulmonary fibrosis model. From the second day, rats in low-and high-dose inter-vention groups were intragastrically treated with 2 mL of 20 and 80 mg · kg-1 emodin, respectively. Predni-sone group were intragastrically administrated with 2 mL of 5 mg·kg-1 prednisone acetate. However, con-trol and model groups were treated with 2 mL of normal saline. All rats were sacrificed on day 28. Pulmonary tissues were then removed, and HE and Masson stai-ning were performed. The contents of hydroxyproline ( HYP ) , malondialdehyde ( MDA ) , superoxide dis-mutase ( SOD) , glutathione-peroxidase ( GSH-Px) and catalase (CAT) in pulmonary tissues were measured. Serum concentrations of tumor necrosis factor-α ( TNF-α) , interleukin ( IL )-6 and IL-17 were detected by enzyme linked immunosorbent assay ( ELISA ) . The expression of Kelch-like ECH-associated protein 1 ( Keap 1 ) , nuclear factor-erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) p65 in pulmo-nary tissues was analyzed using Western blot. Results The pulmonary inflammation and fibrosis in low-and high-dose intervention as well as prednisone groups was significantly improved when compared with model group ( P0. 05 ) . Conclusion Emodin may protect against rats with pulmonary fibrosis by enhan-cing antioxidative ability and inhibiting inflammatory response.