Tanshinone IIA attenuates paraquat-induced acute lung injury by modulating angiotensin-converting enzyme 2/angiotensin-(1-7) in rats

摘要

Tanshinone IIA (TIIA) is an active compound that can be isolated from the Chinese herb, Salvia miltiorrhizae lunge, also known as danshen. Previous studies have demonstrated that TIIA can effectively attenuate bleomycin-induced pulmonary fibrosis in rats. However, it has not been determined whether TIIA can attenuate paraquat (PQ)-induced acute lung injury (ALI). In the present study, the protective effects exhibited by TIIA on PQ-induced ALI, as well as its underlying mechanisms, were investigated using Sprague-Dawley (SD) rats. ALI animal models using rats were established via administration of PQ. Adult male SD rats were randomly divided into three groups: A control group, a PQ group and a PQ + TIIA group. Total cell count, total protein levels and lactic dehydrogenase (LDH) levels in bronchoalveolar lavage fluid (EALF), as well as myeloperoxidase (MPO) activity in lung tissues were determined. Lung histological alterations were also investigated. Angiotensin converting enzyme 2 (ACE2) and Angiotensin 1-7 [Ang-(1-7)] expression levels in the lung were also analyzed. The results demonstrated that administration of PQ induced marked histological alterations, and markedly increased neutrophil infiltration, lung wet/dry weight ratio, total cell count, protein content and L.DH levels in BALF. In addition, PQ was revealed to significantly decrease ACE2 and Ang-(1-7) expression levels in lung tissues. However, it was demonstrated that TIIA attenuated these effects. Therefore, the results of the present study suggest that that TIIA may exhibit a therapeutic effect regarding PQ-induced ALI in rats, and that ACE2 and Ang-(1-7) may be involved in the underlying mechanisms of this effect.