- 學位論文
探討BZD對collagenase誘發小鼠ICH之腦內發炎介質表現與病理變化之作用
Investigation of BZD on the expression of inflammatory mediators and the changes of pathology after intracerebral hemorrhage induced by collagenase in mice
摘要
腦出血為中風其中之一類型，伴隨著高死亡率和癒後不良。直到 目前，腦出血之治療藥物並無有效進展。本篇主要研究BZD 是否可 以改善腦出血之神經功能和發炎情形。 本篇研究顯示在動物實驗中，BZD 可以抑制由collagenase 所引 起小鼠顱內出血所誘導的發炎前驅物之表現及活化如TNF-α及 MMP-9；BZD 亦對腦部發炎引起的血腦屏障通透度增加及腦內出血 後的水腫有顯著改善作用。在動物神經行為學方面，BZD 對於用以 評估腦部神經損傷所導致行為缺陷之神經學分數雖無明顯差異，此表 示BZD 對於神經行為缺陷並無改善之作用，但在小鼠本體感覺與鬍 鬚碰觸的反應BZD 是有顯著的改善的。 然而在臨床上用以評估神經損傷之neuron marker (NSE 及S100β)在給collagenase 誘發小鼠顱內出血後，其蛋白表現量並無顯著上升這可能是由於人體與小鼠生理差異所造成，詳細情況仍須進一步探討釐清才得以清楚。 由上述結果顯示在collagenase 誘發小鼠顱內出血模式中，BZD 可以藉由抑制發炎和降低腦出血後腦水腫來改善腦出血，本篇建議 BZD 對於腦出血之治療可做深入探討研究。
並列摘要
Intracerebral hemorrhage (ICH) is a subtype of stroke with high rates of mortality and associated with poor prognosis. Treatment of intracerebral hemorrhage is often inefficacious; in addition, there is no useful medicine up to now.The purpose of this study was to determine the influence of BZD in improving neurological outcomes and inflammation after intracerebral hemorrhage. In vivo experiments, intracerebral hemorrhage induced inflammatory protein TNF-α and MMP-9 expressions and BZD inhibited those expressions by western blot and zymography; moreover BZD also significant improved blood-brain barrier permeability and cerebral edema in collagenase-induced intracerebral hemorrhage mice model. Besides overall score of eighteen-point composite neurological score had no significant difference, thus the result suggested the neurologic function did not improve. Nevertheless two behaviors of eighteen-point composite neurologic score, that body proprioception and the response to vibrissae touch were significant better in the mice injected BZD. Furthermore NSE and S100β are neuron-damaged markers clinically, but there had no significant difference in collagenase-induced intracerebral hemorrhage mice model. Against that it may be caused by the species difference between people and mice, and the details should be intensive discuss. Above all, our results suggested that BZD inhibited inflammation and reduced cerebral edema in intracerebral hemorrhage, thus BZD had potential effects in intracerebral hemorrhage.