Effects of minocycline on apoptosis and expression of Dickkopf-1, B cell lymphoma/leukemia-2 associated X protein and B cell lymphoma/leukemia-2 in rats with intracerebral hemorrhage

Abstract

Objective To observe the effects of minocycline on neuronal apoptosis and expression of Dickkopf-1 (DKK-1), B cell lymphoma/leukemia-2 associated X protein (bax) and B cell lymphoma/leukemia-2 (bcl-2) after intracerebral hemorrhage in rats. Methods Fifty-four adult male SD rats were randomly divided into sham operation group (n=18), cerebral hemorrhage group (n=18) and minocycline group (n=18). Intracerebral injection of type VII collagenase was used to make cerebral hemorrhage model. The model of cerebral hemorrhage was evaluated by balance beam walking test and turn-around test. The expression levels of bcl-2, bax and DKK-1 proteins in rat brain tissues were detected by immunohistochemistry. Apoptosis of brain tissue around intracerebral hemorrhage in rats was detected by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) apoptosis assay. Results The walking score and turning percentage of balance beam in cerebral hemorrhage group (4.11±0.75) and minocycline group (4.28±0.86) were significantly higher than those in sham operation group (0.50±0.51, P 0.05, P<0.05 1st, 3rd, and 7th day respectively) and DKK-1 (P<0.05) decreased in minocycline group. As compared with sham operation group, the number of apoptotic cells in brain tissue around hemorrhagic site was significantly increased at each time point (1st, 3rd, and 7th day) in intracerebral hemorrhage group [(32.54±5.23), (45.64±4.84), (28.26±2.79) cells, all P<0.01], and that in brain tissue around hemorrhagic site decreased significantly in minocycline group [(15.43±3.04), (23.15±2.49), (17.68±4.54) cells, P<0.05]. The scores of turn-around test (1st, 3rd, and 7th day) in minocycline group was better significantly higher or lower than that in cerebral hemorrhage group (P<0.01). Conclusion Minocycline plays a protective role in rats with cerebral hemorrhage by reducing neuronal apoptosis. Its molecular mechanism may be related to the promotion of bcl-2 and the inhibition of bax expression by reducing DKK-1 expression. Key words: Intracerebral hemorrhage; Dickkopf-1; B cell lymphoma/leukemia-2 associated X protein; B cell lymphoma/leukemia-2; Apoptosis; Minocycline