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Studies on the Mechanisms of Ischemic Preconditioning in Rat and Drug Screening for Protection on Ischemia Injury

Author: ZhangHaiXia
Tutor: ZhangJunTian;DuGuanHua
School: Peking Union Medical College , China
Course: Pharmacology
Keywords: Middle cerebral artery occlusion cerebral ischemia mitochondrion preconditioning reactive oxygen species Na~+-H~+ exchanger calcium overload resazurin MTT proliferation metabolism function GL0108 heat shock protein 27 heat shock protein 70 hippocampus cortex
CLC: R96
Type: PhD thesis
Year: 2003
Downloads: 214
Quote: 0
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Abstract


A brief period of cerebral ischemia confers transient tolerance to a subsequent serious ischemic challenge in the brain. This phenomenon is called ischemic preconditioning. Since the ischemic tolerance afforded by preceding ischemia could hardly be applied on clinic, the mechanism of tolerance has been extensively studied in animals and pharmacological preconditioning emerged as the times require. Pharmacological preconditioning is referred that a drug could induce safe and effective brain tolerance through direct or indirect ways. This concept provides a more powerful tool of screening for neuroprotective compounds.Our study focused on the mechanism of cerebral ischemic preconditioning induced by bilateral carotid arteries occlusion (BCAO). And based on the mechanism, several screening models were set up. Combined with the results obtained in our lab, DL0108 was selected as cerebral protective agent in MCAO model of rat. Also the protective mechanism of DL0108 was primarily studied.Part I: Mechanism of rat cerebral ischemic preconditioning induced by bilateral carotid arteries occlusion.1. Protective effects of ischemic preconditioning on ischemic rat brainIn this experiment, we observed the protective effect of ischemic preconditioning induced by BCAO. Compared with MCAO group, ischemic preconditioning could decrease the infarct area significantly (P<0.001) indicating that ischemic preconditioning could effectively protect the brain function. The staying time on slope board of ischemic preconditioning group was shorter than MCAO group (P<0.001) .The stroke index of ischemic preconditioning group was also reduced.Content of ATP and activity of GSH in ischemic preconditioning group were higher than those of MCAO group (P<0.05、 P<0.01); while contents of MDA、 LA were lower than those of MCAO group (P<0.01、 P<0.05) . Ischemic preconditioning

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