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The Protective Effects of Procyanidin on Ischemiac Brain Injury and Its Mechanisms

Author: CuiMing
Tutor: ZhangYan;ZhangLiRong
School: Zhengzhou University
Course: Pharmacology
Keywords: Procyanidins Cerebral ischemia and reperfusion Inducible nitric oxide synthase Myeloperoxidase Acid -sensitive ion channels
CLC: R285.5
Type: Master's thesis
Year: 2010
Downloads: 73
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Abstract


Objective:Cerebral ischemia, an acute cerebrovascular diseases, is commonly seen in hospital with high mutilation and fatality.However, there is no specific effective medicine for this disease. It is very important for us to find an effective neuroprotective drug to reduce the incidence of residual. Procyanidin (PC) is a kind of natural antioxygen drug which extensively exists in plants. It was demonstrated that PC had the neurons protective effects on cerebral ischemia-reperfusion injury through relieving brain edema. Recently, it has been found that ASICs (acid-sensing ion channels) play an importent role in cerebral ischemia-reperfusion injury. The objective of this study is to investigate the brain-protective effect of PC through testing the activities of iNOS and MPO and the expression of ASIC1a of brain tissue after ischemia-reperfusion in rats which injected with PC.Methods:120 male SD rats (300±50g) were randomly divided into 5 groups:sham group, model group, and PC low dose (50 mg·kg-1), PC middle dose(100 mg·kg-1), PC high dose(200 mg·kg-1) groups. PC groups were injected with PC at the matched concentration at 30 minutes before ischemia. And the rest rats were injected with saline. All rats were given one more time in 2 hours after ischemia.The model of local cerebral ischemia-reperfusion in rats was established with modified sutured-occluded method.All rats were assessed the ethology score after, reperfusion by Zea Longa scoring method. The scoring standard was that:0 point:no notable ethology symptom; 1 point:failure to extend right forepaw fully; 2 point:circling to the right; 3 point: falling to the right; 4 point:couldn’t walk spontaneously and had a depressed level of consciousness.We should reject the dead rats and the ones whose score are 0 point and 4 point. And did the model again to replace the reject rats.After the behavioral test,8 rats in each group were sacrificed for histologic and immunohistochemisty examinations of ASIC la,8 rats were taken to assay the activities of iNOS and MPO, and the rest were used to test the ASIC1a protein expression.Result:①The ethology score in model group is obviously higher than that in sham and PC hige dosage groups (P<0.01). And it is also higher than that in PC low dosage and PC middle dosage groups (P<0.05). And all the PC groups do not have difference on ethology score (P>0.05)②There is no interstitial edema in brain in sham group, and the neurons have normal shape and complete cellular structures. There are interstitial edema and karyopyknosis, karyorrhexis, caryolysis in rat’t brain in model group, and the neurons and gliocyte are obviously swelling. There are different improvement to the above phenomenons in all the PC groups.③The ASIC1 a expression of rat’s brain in model group is as same as that in PC low dosage group (P>0.05), and it is higher than that in sham, PC middle dosage and PC high dosage groups (P<0.05). And there is no difference among all the PC goupes (P>0.05)④The relative gray scale of ASIC1a’s expression in each group are as follow: sham 0.094±0.008,model 0.407±0.008, PC low dosage 0.219±0.014, PC middle dosage 0.207±0.012, PC high dosage 0.195±0.012.The ASIC la expression of rat’s hippocampus in model group is obviously higher than that in sham and all the PC groups (P<0.01). The ASICla expression in PC low dosage group is obviously higher than that in PC high dosage group (P<0.01), it is also higher than that in PC middle dosage group (P<0.05), which is higher than that in PC high dosage group (P<0.05).⑤The activities of iNOS (U·g-1 pro) of each group are as follow:sham 0.458±0.010, model 1.267±0.010, PC low dosage 0.844±0.008, PC middle dosage 0.801±0.009, PC high dosage 0.803±0.011.The activities of iNOS of rat’s brain in model group is obviously higher than that in sham and all the PC groups(P<0.01). There is no difference in PC middle dosage and PC high dosage groups about their iNOS activities (P>0.05),which are obviously lower than that in PC low dosage group(P<0.01).⑥The activities of MPO (U·g-1) of each group are as follow:sham 0.405±0.010, model 0.604±0.011, PC low dosage 0.509±0.009, PC middle dosage 0.501±0.008, PC high dosage 0.501±0.009.The activites of MPO of rat’s brain in model group is obviously higher than that in sham and all the PC groups(P<0.01). All the PC groups have the same level of MPO activities (P>0.05)Conclusions:PC can effectively relieve the cerebral ischemia-reperfusion injury, and its mechanism may be related to the effects of relieving brain edema,antiinflammation, antioxdation and inhibiting the expression of ASIC1a.

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