Protective effect of protopine on the focal cerebral ischaemic injury in rats

Protopine, an isoquinoline alkaloidis, is known to produce many effects such as vasodilation, down-regulation of glutamate levels in brain and decrease of intracellular calcium. However, so far there is no report on the effect of protopine in cerebral ischaemia. In this study, the effect of protopine on the focal cerebral ischaemia was investigated in rats. Male Sprague-Dawley rats were divided into five groups: sham-operated group, vehicle-treated group and three doses of protopine-treated groups (0.98, 1.96 and 3.92 mg/kg). Protopine was intraperitoneally administered to rats once daily for 3 days prior to the ischaemia and 0.9% normal saline to rats in the vehicle-treated group in the same pattern. Rats in the sham-operated group were given 0.9% normal saline without the ischaemia. The focal cerebral ischaemia was induced by the middle cerebral artery occlusion for 24 hr via the intraluminal filament technique. The results showed that pretreatment with protopine reduced the cerebral infarction ratio and serum lactate dehydrogenase activity, and improved the ischaemia-induced neurological deficit score and histological changes of brain in a dose-dependent manner. The further studies demonstrated that protopine increased superoxide dismutase activity in serum, and decreased total calcium and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL)-positive cells in the ischaemic brain tissue in the middle cerebral artery occlusion rats. The results indicate that protopine is able to produce an effective protection on the injury caused by the focal cerebral ischaemia in rats possibly through the multiple effects of calcium antagonism, anti-oxidation and depression of cell apoptosis.