大黄素对肺纤维化大鼠Th1/Th2型细胞因子平衡的影响

Effects of Emodin on the Balance of Th1/Th2 Cytokines in Pulmonary Fibrosis Rats

目的:观察大黄素对博莱霉素所致大鼠肺纤维化的影响,并探讨其是否经调整Th1/Th2型细胞因子平衡起作用。方法:将50只雄性SD大鼠随机分为正常对照组、模型组、大黄素低剂量组、大黄素高剂量组和泼尼松组,每组10只,后4组经气管内注入博莱霉素A5建立大鼠肺纤维化模型,从第2天开始,大黄素低、高剂量干预组大鼠分别予20、80 mg·kg^(-1)大黄素灌胃,泼尼松组以5 mg·kg^(-1)醋酸泼尼松灌胃,其余2组予生理盐水灌胃。建模后第28天处死所有大鼠,取出肺组织行HE染色和Masson染色,用酶联免疫吸附法(ELISA)检测肺组织干扰素-γ(IFN-γ)、白介素-4(IL-4)含量,分离血清,ELISA测定血清IFN-γ、IL-4浓度。结果:大黄素低、高剂量组及泼尼松组肺泡炎症及肺纤维化程度明显轻于模型组(P<0.05 or P<0.01)。与正常对照组比较,模型组肺组织IFN-γ含量、血清IFN-γ浓度、IFN-γ/IL-4比值降低(P<0.01),肺组织IL-4含量、血清IL-4浓度升高(P<0.01);大黄素低、高剂量组及泼尼松组肺组织IFN-γ含量、血清IFN-γ浓度、IFN-γ/IL-4比值高于模型组(P<0.01),而肺组织IL-4含量、血清IL-4浓度低于模型组(P<0.01);大黄素高剂量组、泼尼松组上述指标改善程度优于大黄素低剂量组(P<0.01),但大黄素高剂量组与泼尼松组比较,差异无显著性(P>0.05)。结论:大黄素对博莱霉素所致的肺纤维化大鼠有保护作用,纠正Th1/Th2型细胞因子平衡失调可能是其抗肺纤维化的重要机制。

Objective： To observe the effects of emodin on bleomycin-induced pulmonary fibrosis in rats,and explore whether the effects are mediated by the balance of Th1/Th2 cytokines. Methods： Fifty male SD rats were randomly divided into normal control group,model group,emodin low-dose group,emodin high-dose group,and prednisone group.Each group included 10 animals. Rats in the latter 4 groups were intratracheally administered with bleomycin A5 to establish pulmonary fibrosis model. From the second day on,rats in emodin low-and high-dose groups were intragastrically treated with 20 and 80 mg·kg（-1）emodin,respectively. Rats in prednisone group were intragastrically administrated with5 mg·kg（-1）prednisone acetate,while rats in normal control and model groups were treated with normal saline. All rats were sacrificed on day 28. The pulmonary tissues were removed and used for HE and Masson staining. The contents of interferon-γ（ IFN-γ） and interleukin-4（ IL-4） in pulmonary tissues were detected by enzyme linked immunosorbent assay（ ELISA）. In addition,sera were collected to test IFN-γ and IL-4 concentrations using ELISA. Results： The pulmonary inflammation and fibrosis in emodin low-and high-dose as well as prednisone groups were significantly improved compared to model group（ P〈0. 05 or P〈0. 01）. In comparison with normal control group,pulmonary IFN-γ content,serum IFN-γ concentration and the ratio of IFN-γ to IL-4 were significantly decreased while pulmonary IL-4 content and serum IL-4 concentration were significantly increased in model group（ P〈0. 01）. Pulmonary IFN-γ content,serum IFN-γ concentration and the ratio of IFN-γ to IL-4 were higher in emodin low-and high-dose intervention as well as prednisone groups than model group（ P〈0. 01）,whereas pulmonary IL-4 content and serum IL-4 concentration were lower in emodin low-and high-dose as well as prednisone groups than model group（ P〈0. 01）. The above indicators were significantly improved in emodin high-dose and prednisone groups as compared to emodin low-dose group（ P〈0. 01）. However,there was no significant difference between emodin high-dose group and prednisone group（ P〉0. 05）. Conclusion： Emodin protects rats from pulmonary fibrosis induced by bleomycin. Rectification of Th1/Th2 cytokine balance may be a significant mechanism via which emodin is protective against pulmonary fibrosis.