| Objective: Cerebral ischemia, an acute cerebrovascular diseases, is commonly seen in hospital with high mutilation and fatality. Despite its clinical importance,there is no specific effective medical therapy for this disease. It is therefore important for us to find effective neuroprotective drug to reduce the incidence of residual. At present, an increasing number of researchers began to develop plant amedica as neuroprotective drug, because it has the advantages of containing multiple component, exerting extensive effectiveness, expressing low or no side effects. Procyanidins(PC) is a kind of natural Polyphenols phenolic compound with strong antioxygen function. Recently it was demonstrated that PC has the brain protective effects on cerebral ischemia-reperfusion injury through antioxygen or anti-inflammatory.Cerebral ischemia-reperfusion injury is a complex patho-physiological process. Dysmetabolism is often accompanied, and recent study has revealed that ASICs may play important role role in the course of patho-physiology in cerebral ischemia. But whether PC can affect ASICs and metabolism in ischemia-reperfusion injury is not seen internal and abroad. The objective of this study is to investigate the influence of PC on dysbolism and the expression of ASIC1a of brain tissue after ischemia-reperfusion in rats, so as to further explore the neuro-protective mechanisms of PC and provide theoretical base for application of neuro-protective drugs in clinic.Methods:①160 male SD rats (w=270-300g) were used in this study,and all animals were randomly divided into sham group,model group, PC low-dose group(50mg/kg),middle-dose group(100mg/kg), large-dose group (200mg/kg).Each group has 32 rats. PC were injected by abdomianal cavity at 30 minutes before operation and 2 hours after ischemia, while sham group and model group were given equal NS like above.②The right middle cerebral artery of rats was occluded for 2h and reperfusion was then instituted for 24h by improved Zea-Longa thread block method in rats.③In this study,the evaluations of neurological function were scored by Longa score method. The scoring standard was that: o score: without significant neurology symptom; 1 score: couldn't sufficiently expand left fore-claw; 2 score: turned to the left when walking; 3 score: tumbled to the left when walking; 4: couldn't walk volunteerly and consciousness became weak. The scores could not only reflect pathological course but also were used to select successful models primarily.④The rats were executed after 24 hours reperfusion.Right cerebrum was obtained and some indexes were measured: 8 rats were used to test brain tissue water content with dry-wet quality method; 8 rats were applied to detect pathological changes; 8 rats were selected to measure the content of LD,the activity of Na+-K+-ATPase and Ca2+-ATPase; 8 rats were used to observe the expression of ASIC1a mRNA in hippocampus of rats with RT-PCR method.Results:①The scores of neurological function in model group were higher than that in sham grous (P<0.05) ; while PC middle-dose group and large-dose group showed decreased compared to the model group (P <0.05) ,the low drug group had no difference with model group (P>0.05) .②The water contents in brain tissue in model group were higher than that in sham operation group (P <0.05) ,while they were lower in PC middle-dose group and large-dose group than that in model group(P <0.05), The low-dose drug group had no difference with model group (P>0.05).③There were no dramatical pathological abnormality in sham group.But in model group there were cellular swelling, blurred outline, vacuolus degeneration, cellular nucleus anachromasis, interstitial edema,increasing intercellular space,and decreasing cellular number.There were different level improvement to the above phenomenons in three all PC treated groups, expecially in large-dose group and middle-dose group.④The contents of LD in model group were higher than that in sham group (P <0.05) , while the contents of LD in each PC treated groups were lower than that in model group (P <0.05) .⑤The activity of Na+-K+ATPase in model group were lower than that in sham group (P <0.05); while large-dose group and middle-dose group showed increased compared to model group (P<0.05) , there was no difference in these two drug groups(P <0.05), low-dose group had no difference with the model group (P> 0.05) . The activity of Ca2+ATPase were lower in model group than that in sham operation group (P <0.05), Only in large-dose group were the activity of Ca2+ATPase increased than that in model group (P <0.05). There were no difference in low-dose group and middle-dose group compared with model group (P>0.05) .⑥The expression of ASIC1a mRNA was increased in model group compared to sham operation group (P <0.01), while the expression of ASIC1a mRNA was decreased in PC large-dose group contrast to model group(P <0.05), there was no difference in the low and middle PC groups compared to the model group (P>0.05) .Conclusions①PC can reduce cerebral ischemia-reperfusion damages in rats and has an neuroprotective effect.②The probable neuroprotective mechanism of PC is associated with protecting neuro-function, decreasing brain edema, improving brain cell metabolism and inhibiting the expression of ASIC1a channel. |
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