Effect of cholecystokinin-octapeptide on focal cerebral ischemia/reperfusion injury in rats |
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Authors: | YANG Shi-fang LING Yi-ling LING Yi-qun DUAN Guo-chen WANG Jian-qin |
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Institution: | Department of pathophysiology, Hebei Medical University, Shijiazhuang 050017, China |
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Abstract: | AIM:To examine the effect of cholecystokinin-octapeptide (CCK-8) on focal cerebral ischemia/reperfusion injury and its underlying mechanisms.METHODS:By using the suture model of focal cerebral ischemia and reperfusion, the effects of intracerebroventricular (icv) injection of CCK-8 and proglumide, nonselective CCK receptors antagonist, on the infarct size, regional cerebral blood flow (rCBF), and the levels of nitric oxide (NO), malondialdehyde (MDA) were observed in different brain regions of rats subjected to 1 h focal cerebral ischemia followed by 24 h reperfusion.RESULTS:(1) pretreatment with different doses of CCK-8 (0.3 μg,1.0 μg,2.0 μg or 4.0 μg) could attenuate the infarct size, but the statistically significant effects of CCK-8 were obtained only at the doses of 1.0 μg and 2.0 μg(P<0.05). The neuroprotective effects of CCK-8 were blocked by pretreatment with proglumide. Administration of proglumide alone could worsen the ischemia/reperfusion injury. (2) CCK-8 (1.0 μg) inhibited the increase in NO, MDA levels in the ischemic core, and also inhibited the increase in NO level in the ischemic penumbra. The rCBF in the CCK-8 group was significantly higher than the normal value at 24 h after reperfusion (P<0.05).CONCLUSIONS:These results suggest that both endogenous and exogenous CCK-8 alleviate focal cerebral ischemia/reperfusion injury. Such an action may be associated with inhibition of free radical-induced injuries and the improvement in rCBF. |
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Keywords: | Cholecystokinin Brain ischemia Nitric oxide Malondialdehyde Cerebral blood flow |
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