Neuro-protective effect of harpagide on acute cerebral ischemic injury in mice and its mechanism involving mitochondria / 中国药学杂志

ABSTRACT

OBJECTIVE: To observe the neuro-protective effects of harpagide on acute cerebral ischemic injury in mice and its mechanism involving mitochondria. METHODS: Acute cerebral ischemia were achieved by operation of MCAO in the left brain, random allocation was taken to divide ICR mice into sham group, model group, nimodipine group and harpagide (5,10,15 mg·kg-1) groups. Mice were intraperitoneal injected harpagide immediately after surgeiy. Nerve function score, content of brain water, brain index and the common changes of brain pathological structure in HE staining were measured Ability of mitochondria Ca2+-Mg2+-AT-Pase and protein expression level of caspase-3 in the MCAO mice' brains was determined Ultrastructure change of mitochondria under the TEM was observed. RESULTS: Compared with model group, the harpagide groups could decreased the nerve function score, the content of brain water, brain index and the volume of ischemia in mice with different degrees in MCAO mice (P-1 of harpagide could increased the activity of Ca2+-Mg2+-ATPase obviously (P<0.01) And significantly decreased the protein expression level of caspase-3 (P<0.01) harpagide groups could protect the pathogeny structure and the ultrastructure of mitochondria with different degrees in MCAO mice, decrease edema of mitochondria obviously. CONCLUSION: Harpagide could obviously protect acute cerebral ischemia in mice, its therapeutical effects are approached to protecting the activity of brain mitochondria and decreasing protein expression level of caspase-3.