Effects of Hemin on cognitive function and the expression of neuroglobin in rats with vascular dementia

Abstract

Objective To observe the influence of Hemin on both the expression of neuroglobin (Ngb) and Tau protein phosphorylation in rats with vascular dementia (VD), and explore the effect and mechanism of Ngb in VD. Methods VD model was established in rats with a permanent bilateral common carotid arteries occlusion(2-VO). Fifty four healthy male SD rats were randomly divided into 3 groups: sham operation group, VD group and Hemin group. According to ischemic time, the animals in each group were randomly allocated into 1 week subgroup, 4 weeks subgroup and 8 weeks subgroup(n=6 in each subgroup). The learning and memory ability of rats were evaluated by Morris water maze test.The brain histopathological changes were observed by HE staining and the expression of Ngb and phosphorylated Tau (p-Tau) was determined by Western blot. Results Compared with the sham operation group, after 2-VO the escape latency extended (all P<0.05) and cross-platform performance reduced in rats in both VD group and Hemin group(all P<0.05). The learning and memory ability of rats in Hemin group was better than that in VD group at the corresponding time point: the increase in the number of crossing platforms(1 week: Hemin group (7.00±0.89) times vs VD group (5.50±1.22) times, t=2.42, P<0.05; 4 weeks: Hemin group (5.33±0.52) times vs VD group (3.50±1.04) times, t=3.84, P<0.01; 8 weeks: Hemin group (6.50±0.55) times vs VD group (4.50±1.05) times, t=4.14, P<0.01). The expression of Ngb and phosphorylated Tau (p-Tau) increased in VD group and Hemin group (P<0.01). Compared with VD group, the expression of Ngb in Hemin group was increased(1 week: Hemin group (3.45±0.23) vs VD group (2.56±0.08), t=5.67, P<0.01; 4 weeks: Hemin group (3.08±0.13) vs VD group (2.28±0.08), t=7.96, P<0.01; 8 weeks: Hemin group (2.82±0.12) vs VD group (2.05±0.10), t=7.28, P<0.01), while p-Tau was decreased (1 week: Hemin group (1.57±0.12) vs VD group (2.40±0.15), t=7.62, P<0.01; 4 weeks: Hemin group (2.14±0.21) vs VD group (3.18±0.14), t=8.23, P<0.01; 8 weeks: Hemin group (1.83±0.13) vs VD group (2.79±0.19), t=4.91, P<0.01). In VD group and Hemin group, the learning and memory ability exhibited a negative correlation with Ngb (r=-0.892, P<0.01), whereas a positive correlation with p-Tau (r=0.932, P<0.01). Conclusion Hemin induces high expression of Ngb and inhibits Tau phosphorylation in VD rats. Ngb may play a neuroprotective role in the development of VD by regulating Tau phosphorylation. Key words: Hemin; Neuroglobin; Tau; Vascular dementia; Cognitive function; Rat