| 목적 : The management of Graves’ orbitoopathy (GO) is challenging and often not satisfactory, as no reliable, specific, and safe medical therapeutic agents have not been developed. Tanshinone IIA, a lipophilic diterpene, is suggested to have anti-adipogenic and antioxidant properties. We investigated the therapeutic effect of tanshinone IIA in primary cultures of orbital fibroblasts in nontoxic concentrations and the signaling pathway involved.방법 : To evaluate anti-adipogenic activites, fibroblasts were subjected to differentiation protocol including peroxisome proliferator activator gamma (PPARγ) agonist for 10 days, and exposed to tanshinone IIA during adipocyte differentiation. Differentiated cells were stained with oil red O, and expression of adipogenesis-related factors, PPARγ and CCAAT-enhancer-binding proteins (C/EBP) α, β were determined by western blot. Anti-oxidant activities were investigated by measuring intracellular ROS generation and heme oxygenase-1 (HO-1) expression. Involved signaling pathway was also investigated.결과 : Tanshinone IIA showed a dose-dependent effect in decreasing ROS levels and up-regulated HO-1 protein expression in a time and dose dependent manner (P<0.001). Adipogenesis was also inhibited by tanshinone IIA in a dose-dependent manner (P<0.001), presented by Oil Red O stain and decreased expression of PPARγ and C/EBP α, β in western blot analysis. Treatment of orbital fibroblasts with tanshinone IIA (10uM) increased phosphorylated extracellular signal-regulated kinase (pERK) and an ERK inhibitor (PD98059) significantly blocked tanshinone IIA induced HO-1 upregulation.결론 : Our study results suggest that tanshinone IIA possess significant anti-oxidative and anti-adipogenic effects in primary orbital fibroblast. Activation of ERK signaling pathway is required for tanshinone-induction of HO-1 protein expression in orbital fibroblasts. These results may provide a basis for further study of the potential usage of tanshinone IIA for the treatment of Graves’ ophthalmopathy. |