Lung Protective Mechanism of Compound Kushen Injection on Radiation-induced Pulmonary Injury / 中国实验方剂学杂志

ABSTRACT

Objective:To observe the effect of compound Kushen injection on the expressions of transforming growth factor-β1 (TGF-β1), drosophila mothers against decapentaplegic protein 3 (Smad3), glycogen synthase kinase-3β (GSK-3β) and β-catenin mice models with radiation-induced pulmonary injury (RIPI), in order to explore its possible mechanism of action. Method:On XStrahl precision radiation research platform for small animals (SARRP), a single 20 Gy bilateral lung field irradiation was performed to establish a mice model of RIPI. Thirty-two mice were randomly divided into normal control group, model group, compound Kushen injection group and dexamethasone injection group. The normal control group and the model group were given an equal volume of 0.9%sodium chloride solution and injected intraperitoneally for 4 weeks. The pathology of lung tissue tissues was observed by using hematoxylin-eosin (HE) staining. Immunohistochemical(IHC) was used to detect the expressions of E-cadheren and Vimentin proteins in mice lung tissues.Real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expressions of TGF-β1, Smad3, GSK-3β and β-cateninin.Western blot was used to detect the protein expressions of TGF-β1, Smad3, GSK-3β and β-cateninin. Result:Compared with the normal group, the pulmonary coefficient of the model group was significantly decreased (P<0.01). Inflammatory cell infiltration, pulmonary interstitial edema, congestion, destruction of alveolar structure and partial alveolar atrophy were observed in the lung tissues of the model group. Compared with the model group, in the compound Kushen injection group, the levels of infiltration of lung inflammatory cells and pulmonary interstitial lesions in mice, the expression of Vimentin in lung tissues (P<0.01), and the expressions of TGF-β1, Smad3, GSK-3β and β-cateninin were significantly decreased (P<0.01), whereas the expression of E-cadheren was significantly increased (P<0.01). However, compared with the dexamethasone injection group, in the compound Kushen injection group, the pathological changes of lung tissues were similar, and the expression levels of E-cadheren, Vimentin, TGF-β1, Smad3, GSK-3β and β-cateninin were not significantly different. Conclusion:Compound Kushen injection can alleviate pulmonary fibrosis of lung in the treatment of RIPI, and the mechanism may be associated with inhibiting the mRNA and protein expressions of TGF-β1, Smad3, GSK-3β and β-catenin related to epithelial-mesenchymal transition(EMT), promoting the expression of E-cadheren, and inhibiting the expression of Vimentin, so as to inhibit the occurrence of EMT.