Oxymatrine exerts a protective effect in myocardial ischemia/reperfusion-induced acute lung injury by inhibiting autophagy in diabetic rats

摘要

Oxymatrine (OMT) is the primary active component of Sophora flavescens Ait., and is widely used for the treatment of diabetic complications. The present study aimed to investigate the effects of OMT on acute lung injury (ALI) in diabetic rats subjected to myocardial ischemia/reperfusion (I/R). ALI in a myocardial I/R model was established in streptozocin-induced diabetic rats. Enzyme-linked immunosorbent assays were used to evaluate the levels of creatine kinase isoenzyme MB and lactate dehydrogenase, and the inflammatory response was assessed via leukocyte counts and the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8 in the bronchoalveolar lavage (BAL) fluid. Hematoxylin and eosin staining was used to determine pathological changes to the lung tissue, and the autophagy-related proteins LC-3II/LC-3I, Beclin-1, autophagy protein 5 (Atg5) and p62 were detected by western blotting. Diabetic rats subjected to myocardial I/R showed increased levels of ALI with a higher lung injury score and WET/DRY ratio, and lower partial pressure of oxygen. This was accompanied by aberrant autophagy, indicated by an increased LC-3II/LC-3I ratio, decreased p62 expression levels, increased Atg5 and beclin-1 expression levels, decreased superoxide dismutase activity and increased 15-F2t-isoprostane formation in lung tissues, as well as increased levels of leukocytes, TNF-alpha, IL-6 and IL-8 in the BAL fluid. Administration of the autophagy inducer rapamycin significantly accelerated these alterations, while the autophagy inhibitor 3-Methyladenine exerted the opposite effects. These results indicated that diabetic lungs are more vulnerable to myocardial I/R, which was associated with aberrant autophagy. Furthermore, oxymatrine was observed to reverse and alleviate ALI in diabetic rats with myocardial I/R in a concentration-dependent manner, the mechanism of which may be associated with the inhibition of autophagy.