Combination Therapy of Wuweizi (Schisandrae Chinensis Fructus) and Dexamethasone Alleviated Dexamethasone-Induced Glucocorticoid Osteoporosis in Rats with Idiopathic Pulmonary Fibrosis

Abstract

Objective. To investigate the therapeutic effect of combined application of Wuweizi (Schisandrae Chinensis Fructus) and dexamethasone in rats with idiopathic pulmonary fibrosis (IPF) and the possible protective effect of Wuweizi against dexamethasone-induced glucocorticoid osteoporosis (GIOP). Methods. There were five groups in this study, including the sham operation group, model group, Wuweizi group, dexamethasone group, and the combination group. A rat IPF model was made by the endotracheal injection of bleomycin. After modeling, rats were given drug interventions for 7 and 28 days. Rats were sacrificed for pathological morphology examination of the bone and lung and quantitative determination of biochemical markers of bone metabolism and angiogenesis-related cytokine to observe therapeutic efficacy on the 7th and 28th day. ELISA was used for the quantitative determination of tartrate-resistant acid phosphatase (TRACP), bone alkaline phosphatase (BALP), hypoxia-inducible factor (HIF-1α), platelet-derived growth factor (PDGF), pigment epithelium-derived factor (PEDF), and endostatin in serum. The concentrations of calcium (Ca) and phosphorus (P) were detected with the automatic biochemical analyzer. Results. After drug interventions for 7 and 28 days, alveolitis and pulmonary fibrosis in treatment groups showed significant improvement compared with those in the model group (P<0.05). Bone histopathological figures showed severely damaged trabecular bone and bone marrow cavity in the dexamethasone group, but it was significantly alleviated in the combination group. The concentrations of BALP and Ca in the combination group were significantly higher than those in the dexamethasone group after treatment, while the concentrations of TRACP and P were lower than those in the dexamethasone group (P<0.05). The concentrations of HIF-1α and PDGF in treatment groups were significantly lower (P<0.05) compared with those in the model group, while PEDF and endostatin were increased (P<0.01). However, the concentration of HIF-1α in the combination group was higher than that in the dexamethasone group, and the concentration of PEDF was lower than that in the dexamethasone group. Conclusions. The combination therapy of Wuweizi and dexamethasone effectively treated IPF rats by regulating angiogenesis, meanwhile distinctly alleviating dexamethasone-induced GIOP.