| Summary: | 碩士 === 臺北醫學大學 === 醫學科學研究所 === 98 === Stroke is a leading cause of mortality and morbidity in developed countries. Stroke can be divided into 2 entities: ischemic or hermorrhagic. The incidence of ischemic stroke is higher than hermorrhagic type. The pathophysiological mechanisms of brain injury after focal ischemia have been investigated widely, but the development of novel treatment agents for acute ischemic stroke has not progressed as well. One strategy for treating acute stroke patients is the neuroprotective agents. Unfortunately, clinical trials using various neuroprotective agents for ischemic/ reperfusion injury are still ineffectual. Because the middle cerebral artery is the vessel mostly occluded in ischemic stroke, so the middle cerebral artery ischemia/ reperfusion of rodents provides an excellent animal model that is relevant to ischemic stroke in human.
Hinokitiol, also known as β-thujaplicin, is a tropolone-related compound found in the heart wood of several cupressaceous plants. It has a wide variety of biological functions, including anti-oxidative, anti-inflammatory, and iron chelating activities. However, the ability of hinokitiol to protect neuronal cells from ischemia/reperfusion injury has not been studied so far.
Study goal of the thesis was therefore to evaluate the neuroprotective effects of hinokitiol in a cerebral ischemia-reperfusion injury animal model, and the inhibitory effects on inflammatory response and expression of apoptosis. We tested the effects of hinokitiol in transient focal cerebral ischemia and reperfusion rat model. Hinokitiol (0.2 mg/kg i.p. and 0.5 mg/kg i.p.) markedly attenuated the infarct volume about 25.15 % and 49.59 % respectively at 24 hours after middle cerebral artery occlusion. Subsequently, we examined the neuropreotective mechanisms of hinokitiol in the molecular and cellular pathophysiology of brain injury after focal ischemia. In western blotting, we found that pretreatment with hinokitiol may significantly reduce the expression of iNOS, HIF-1α, TNF-α and caspase-3.
According to these findings, hinokitiol has neuroprotective effects against cerebral ischemia and reperfusion injury. Moreover, the beneficial results may be due to the reduction of iNOS, the suppression of pro-inflammatoy cytokine TNF-α and the inhibition of apoptotic of caspase-3 and HIF-1α. However, the exact mechanisms of their neuroprotective effects at cellular signal transduction need to be clarified in the future.
|
|---|
