清肺方对结缔组织病相关间质性肺炎模型大鼠抗纤维化作用的实验研究

Experimental Study on the Effect of Qingfei Decoction in Antifibrosis in Rats with Connective Tissue Disease Related Interstitial Pneumonia

[目的]通过博来霉素(bleomycin,BLM)诱导建立结缔组织病相关间质性肺炎大鼠模型,探讨清肺方对间质性肺炎大鼠的抗纤维化作用。[方法]清洁级SD大鼠48只,雄性,体质量为180~200g,适应性饲养1周后,分为正常对照组、间质性肺炎模型组、强的松组和清肺方组,每组12只。除正常对照组外,其余各组通过气管内灌注5mg·kg-1 BLM诱导建立大鼠间质性肺炎动物模型。用药28d后,对比清肺方组与间质性肺炎模型组、强的松组、正常对照组之间的肺组织染色及纤维化评分,检测肺组织羟脯氨酸(hydroxyproline,HYP)含量、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白介素-6(interleukin-6,IL-6)、转化生长因子β1(transforming growth factor,TGF-β1)。[结果](1)病理染色发现:与正常对照组比较,间质性肺炎模型组大鼠肺组织结构破坏,重度炎性细胞浸润,大块的纤维组织增生实变,肺泡腔内分布胶原纤维病灶;与间质性肺炎模型组比较,清肺方组大鼠肺组织损害减轻,炎性细胞浸润减少,纤维组织增生减少,胶原相对面积较模型组明显减少。(2)与正常对照组比较,各模型组大鼠肺组织HYP含量明显升高,且差异有统计学意义(P<0.01);与间质性肺炎模型组相比,清肺方组大鼠肺组织HYP含量明显降低,且差异具有统计学意义(P<0.01)。(3)与正常对照组比较,各模型组大鼠肺组织匀浆TNF-α、IL-6、TGF-β1浓度明显升高(P<0.05,P<0.01);与间质性肺炎模型组比较,清肺方组大鼠肺组织匀浆TNF-α、IL-6、TGF-β1浓度明显降低(P<0.05,P<0.01)。[结论]1.清肺方对BLM诱导的大鼠间质性肺炎、肺纤维化有抑制作用。2.清肺方对BLM诱导的大鼠间质性肺炎的抑制作用机制可能与TNF-α、IL-6、TGF-β1有关。

[Objective]To establish a rat model of connective tissue disease associated interstitial pneumonia induced by bleomycin, and explore the effect of Qingfei Decoction on interstitial pneumonia and its effect on antifibrosis. [Methods]48 male SD rats, weight 180~200 g. All the rats were fed adaptivelly for one week and the rat model of interstitial lung disease were established by means of pour 5 mg·kg-1 BLM into trachea.Divided these rats into 4 groups：the normal control group, the interstitial pneumonia model group,the predmisone group and the Qingfei Decoction group. In addition, each group 12 rats.After 28 days＇ medication, compare the pathological difference between Qingfei Decoction group with the interstitial pneumonia model group, the predmisone group and the normal control group, and the difference in the expressions of TNF-α, IL-6, TGF-β1 in lung tissue, and the expression of hydroxyproline in lung tissue. [Result]（1）Pathological staining showed that： compared with the normal control group, the destruction of lung tissue structure of rats pneumonia, severe inflammatory cell infiltration, fibrous tissue hyperplasia massive consolidation, alveolar distribution of collagen fiber lesions in model groups; compared with interstitial pneumonia model group, Qingfei Decoction group reduced lung tissue damage, reduce inflammation cell infiltration, fibrous tissue hyperplasia reduced collagen relative area decreased compared with model group.（2） Compared with normal control group, the lung tissue of HYP rats was significantly increased, and the difference was statistically significant the model group（ P〈0.01）; Compared with interstitial pneumonia in the model group, the content of HYP in lung tissue of rats Qingfei Decoction group decreased significantly, and the difference was statistically significant（P〈0.01）.（3）Compared with normal control group, the model group of rat lung tissue IL-6, TNF-alpha, TGF-beta1 concentration increased significantly（P〈0.05, P0.01）; compared with the model group, interstitial pneumonia, Qingfeifang lung tissue homogenate TNF-alpha, TGF-beta1, IL-6 concentration decreased significantly（P〈0.05, P0.01）. [Conclusion]1.Qingfei Decoction has inhibition effect to the bleomycin induced interstitial pneumonia.2.The treatment mechanism of Qingfei Decoction to BLM-ILD maybe related to TNF-α, IL-6, TGF-β1.