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The Neuroprotective Effects Of Shenqi Fuzheng Solution And The Role Of Protein Kinase C In The Formation Of Ischemic Tolerance Induced By Isoflurane Preconditioning Against Ischemia/Reperfusion Injury In The Brain

Posted on:2006-05-04Degree:MasterType:Thesis
Country:ChinaCandidate:N XuFull Text:PDF
GTID:2144360152996306Subject:Anesthesia
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Since Kitagawa and his colleagues firstly reported the phenomenon that ischemic preconditioning can induce ischemic tolerance in the model of global cerebral ischemic gerbil in 1990, investigators have been keeping on trying to find non-ischemic preconditioning methods. We have been devoted to the study in neuroprotection for a long time. While looking for the possible drugs with neuroprotective effects, we also search into the mechanisms of cerebral ischemic tolerance induced by non-ischemic preconditioning and wish to find some feasible methods for clinical application. The Traditional Chinese Medicines are proved to be effective with low poisonous and side effects. Thus a plenty of studies have been done on their neuroprotective effects in recent years and many drugs are proved to be able to protect the brain against ischemic injury. Shenqi Fuzheng solution is an intravenous mixture made of Radix Codonopsis and Radix Atragali, which can improve the body immunity. It is lack of scientific foundation that Shenqi Fuzheng Solution has neuroprotectiveeffects. In our previous studies, we have found that isoflurane, one of commonly used volatile anesthetics in clinic, can induce cerebral ischemic tolerance. And ATP-sensitive potassium channel (Katp) and adenosine A1 receptor probably play key roles in the mechanisms of isoflurane preconditioning. This study was designed to determine the neuroprotective effects of Shenqi Fuzheng solution and to investigate the role of protein kinase C in the formation of acute ischemic tolerance induced by isoflurane preconditioning against ischemia/reperfusion injury in the brain.Part I The Neuroprotective Effects of Shenqi Fuzheng SolutionObjectiveTo investigate the neuroprotective effects of Shenqi Fuzheng solution against transient focal cerebral ischemic injury in rats.MethodsThirty male SD rats were randomly divided into 3 groups(n=10 in each group): Control group received intraperitoneal injection of normal saline 25ml ? kg-1 30min before middle cerebral artery occlusion (MCAO), the Shen-pre group received intraperitoneal injection of Shenqi Fuzheng solution 25ml ? kg-1 30min before MCAO, and the Shen-post group received intraperitoneal injection of Shenqi Fuzheng solution 25ml ? kg-1 120min after MCAO. The neurological outcome was evaluated at 24h after reperfusion. The infarct volume was then assessed with TTC staining after the neurological outcome evaluation.Infarct volume of brain: The infarct volume of brain in Control group(278.0 ± 92.1mm3) was significantly larger than those in Shen-pre(138.1±47.0mm3, P=0.000) and Shen-post(179.2±61.8mm3, P=0.004) group. There were no statistical differences between the Shen-pre and Shen-post groups(P=0.197).Neurological deficit scores(NDS): There were statistical differences among 3 groups(P<0.05).Part Ⅱ The Role of Protein Kinase C in the Formation of AcuteIschemic Tolerance Induced by Isoflurane Preconditioning againstIschemia/Reperfusion Injury in the BrainObjectiveTo investigate the role of protein kinase C(PKC) in the formation of acute cerebral ischemic tolerance induced by isoflurane preconditioning in rats.MethodsSixty male SD rats were randomly divided into 6 groups(n=10 in each group): Control group and Che group: animals in both groups received 98% O2 for 60min and the Che group were intracerebroventricularly(ICV) injected Che(2 μ g/10 μ 1) before O2 inhalation; Iso group, Iso+Che group, Iso+Vehicle group and Sham group: animals in 4 groups received 98% O2 in 1.5% Iso for 60min, and the Iso+Che and Iso+Vehicle groups were ICV injected Che(2 μ g/10 μ 1) or normal saline(10 μ 1) respectively before Iso preconditioning; while animals in Sham group simply received the surgery of ICV injection before Iso preconditioning. 60min after pretreatment, all the animals were subjectd to right middle cerebral artery occlusion(MCAO)...
Keywords/Search Tags:cerebral ischemia, preconditioning, middle cerebral artery occlusion, ischemia-reperfusion, Shenqi Fuzheng solution, isoflurane, protein kinanse C
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