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目的:观察滋阴基础上的清热化痰与益气活血序贯疗法对IPF小鼠肺组织形态学,血清中IL-6、TGF-β含量的影响。方法:SPF级ICR雄性小鼠105只,体重16~20 g,随机分为正常对照组、模型组、西药治疗组以及4个中药治疗组,每组15只,除正常对照组外,其余各组采用气管内注射博莱霉素(5 mg/kg)复制小鼠肺纤维化模型。造模第2天起,正常对照组和模型组用生理盐水灌胃,西药组按0.15 mg/g给予甲基泼尼松。4个中药治疗组分别按照不同阶段不同药物不同时限给药,于21 d处死小鼠。HE染色及武兆发简化Mallory氏胶原染色,观察肺组织形态变化;双抗夹心酶联免疫吸附试验(ELISA)法检测血清中IL-6、TGF-β的含量。结果:HE染色及胶原染色显示,模型组小鼠支气管周围及肺泡间隔有大量炎症细胞浸润并伴有出血性渗出,纤维化程度明显。西药组较模型组虽好转但效果不及中药组明显。中药12组肺泡炎明显好转,肺泡内未见明显的炎性细胞,肺泡隔、细小支气管周围的纤维化病灶较模型组有明显改善,肺泡结构已基本恢复。模型组小鼠血清中IL-6、TGF-β含量均高于正常组,与模型组比较,中药12组小鼠血清中IL-6、TGF-β含量降低显著。结论:从以上各项实验指标观察来看,中药12组能明显控制与改善肺纤维化,降低炎症细胞因子IL-6、TGF-β的含量,提示清热化痰药适宜在肺纤维化早期使用,不宜贯穿使用于整个病程,益气活血药可在病程中后期使用。
Objective: To observe the effect of clearing away heat and eliminating phlegm and sequential therapy of invigorating Qi and activating blood on the morphology of lung and serum levels of IL-6 and TGF-β in IPF mice. Methods: 105 male SPF ICR mice weighing 16-20 g were randomly divided into normal control group, model group, western medicine treatment group and four Chinese medicine treatment groups, with 15 rats in each group. Except normal control group, Group A mice model of pulmonary fibrosis was reproduced by intratracheal injection of bleomycin (5 mg / kg). On the second day after model establishment, the normal control group and the model group were given gavage with saline, and the western medicine group was given methylprednisone at 0.15 mg / g. Four Chinese medicine treatment groups were administered with different drugs in different stages according to different time points, and mice were sacrificed at 21 days. HE staining and Wuzhao hair were used to simplify Mallory’s collagen staining, and the morphological changes of lung tissue were observed. The contents of IL-6 and TGF-β in serum were detected by ELISA. Results: Hematoxylin and eosin staining and collagen staining showed that there was a large number of infiltration of inflammatory cells and hemorrhagic exudation around the bronchial and alveolar septum of mice in the model group with a significant degree of fibrosis. Western medicine group than the model group improved but the effect is less obvious than the traditional Chinese medicine group. The alveolitis of 12 groups of Chinese medicine was obviously improved. No obvious inflammatory cells were found in the alveoli. The fibrosis lesions around the alveolar septa and the fine bronchi were significantly improved compared with the model group, and the alveolar structure had basically recovered. The levels of IL-6 and TGF-β in serum of model group were higher than those of normal group. Compared with model group, the content of IL-6 and TGF-β in serum decreased significantly in 12 groups. Conclusion: From the above experimental indicators of observation, the 12 groups of Chinese medicine can significantly control and improve pulmonary fibrosis and reduce the levels of inflammatory cytokines IL-6, TGF-β, suggesting that Qingre phlegm suitable for early use of pulmonary fibrosis , Should not be used throughout the course of the disease, Yiqihuoxue medicine in the late course of use.