Tanshinone II A improves apoptosis and oxidative stress of Schwann cells induced by intermittent high glucose in suckling rats

Abstract

Objective To investigate the effects of tanshinone ⅡA (Tan ⅡA) on the intermittent high glucose (IHG)-induced oxidative stress and apoptosis of Schwann cells (SCs) in suckling rat. Methods Cultured SCs of newborn suckling rats were randomized into several groups including control (con, 5.6 mmol/L glucose), stable high glucose (HG, 50 mmol/L glucose), IHG (5.6 and 50.0 mmol/L glucoseper 8 h alternative), osmotic control, ALA (500 μmol/L) and IHG in the presence of 0.1, 1.0, 10.0 μmol/L Tan Ⅱ A. Apoptosis rate, oxidative stress level, expression of apoptosis related proteins and the mRNA in the cells were detected. Results (1) The percentages of apoptotic cells exposed to HG ((34.57± 2.45)%) and IHG ((40.17±2.33)%) were significantly higher than that in control group ((4.74±0.26)%). Furthermore, apoptosis rate of IHG was much higher than that of HG (t=3.70, P<0.01). (2) ROS and 8-OHdG levels increased significantly in the IHG group compared with those in control and HG groups (F=73.44, 194.21, P<0.01). IHG exposure up-regulated expression of bax protein and mRNA (F=66.78, 126.69, both P<0.01), while down-regulating expression of bcl-2 protein and mRNA (F=151.88, 54.99, both P<0.01). In addition, IHG increased activities of caspase-3 and (poly(ADP-ribose) polymerase, PARP) (129% , 18% , 139% , 56% , all P<0.01). (3) Treatment with 1.0 μmol/L and 10.0 μmol/L of Tan IIA inhibited IHG-enhanced ROS production and 8-OHdG levels (t=3.50-6.47, P<0.05). Bax protein and mRNA (t=3.59-5.39, P<0.01), PARP and caspase-3 activation (42%, 61%, 13%, 34%, all P<0.01), and SC apoptosis (t= 12.39, 21.26, P<0.01)were decreased with Tan ⅡA, too. Conclusions Tan ⅡA decreases IHG-induced apoptosis via reducing oxidative stressin SCs of newborn suckling rats. Key words: Oxidative stress; Apoptosis; Intermittent high glucose; Schwann cells; Tanshinone ⅡA