| 摘要: | Heat stroke was induced by placing urethane-anesthetized rats in the hot chamber with 42℃ ambient temperature. Instead, the normothermic control rats were placed in chamber with room temperature, 24℃. The onset of the rapidly decreased mean arterial pressure (MAP) and cerebral blood flow (CBF) from peak level was defined as the onset of heat stroke. And the interval from the onset of heat stroke to cardiac arrest was defined as the survival time (ST) of rats. The values of MAP and CBF after heat stroke onset were significantly lower than those in control rats. However, plasma levels of tumor necrosis factor-α (TNF-α) were higher. Extracellular concentration of glutamate and lactate/pyruvate ratio (cellular ischemia markers), and glycerol (a cellular injury marker) in the corpus striatum were markedly greater. The role of ET-1 in the pathological manifestations of heat stroke is worth further study. Effects following endothelin B (ETB) receptor activation (but not ETA receptor) by ET-1 on cytokine production of human monocytes with 7-fold higher release of TNF-α, compared to another cytokines. There were sufficient evidences to show that high levels of TNF-α not only resulted multi-organ dysfunction via inflammatory response and led to shorten the survival time of heat stroke animals, but were closely associated with cardiac function in various cardiovascular disorders. Additionally, there was less attention to clarify in detail the effective on heat stroke with ETBR antagonists. Therefore, in present study, we attempted to investigate effects of acute treatment or pretreatment with an ETBR antagonist (BQ 788) on heat stroke-induced pathophysiologic changes (including arterial hypotension, cerebral ischemia, and neuronal damage) and survival in a rat model. In present study, our results suggest that heat stroke induced low SBF, high levels of plasma TNF-α, arterial hypotension, cerebral ischemia, neuronal damage, and a decrease in survival time in rats. We tried to give BQ 788 immediately or beforehand, and expect to be able to improve the heat stroke-induced arterial hypotension, cerebral ischemia, and neuronal damage, and eventually resulted in prolongation of the survival time; however, ETBR antagonist, showed no efficacy in those lesions and symptoms. Our investigations implicate that the pretreatment or treatment with ETBR may have no efficiency to diminish the damage and pathological formation of heat stroke in a rat model.
將urethane 麻醉後大鼠置於42℃溫箱中誘發熱中風之生成，而常溫控制組大鼠則置於室溫24℃的溫箱中。當熱中風誘發生成過程中，大鼠平均動脈壓和腦血流數值從至高點瞬間滑落之時間點，視為熱中風生成點，而從熱中風生成點起至大鼠心跳停止的期間則視為熱中風存活時間。大鼠的平均動脈壓和腦血流數值於熱中風生成後顯著的比常溫控制組大鼠低落，而血漿中腫瘤壞死因子-阿爾法(TNF-α)則明顯升高，於腦中紋狀體中胞外麩胺酸和丙酮酸/乳酸比值(細胞缺血指標)和甘油(細胞損傷指標)顯著上升。內皮素-1 於熱中風病理生成過程被認為是值得深入探討的。研究指出於人體單核球中內皮素-1 作用生成細胞介質素，主要是透過內皮素B 受體的作用(而非內皮素A 受體)，且相對於其他細胞介質素生成，可誘發產生七倍高的TNF-α。有許多證據也指出於熱中風動物體中高濃度的TNF-α不僅會透過發炎反應導致多發性器官功能失調，而會縮短熱中風存活時間，並且在許多心血管疾病中與心臟功能有密切關係。另外，也鮮少有針對內皮素B 受體拮抗劑對熱中風之影響的詳細研究。因此，現今的實驗中，我們試圖探討給大鼠急性投予和前處理內皮素B 受體拮抗劑(BQ 788)對熱中風所致生理病理改變(包括動脈壓低落、腦缺血與神經損傷)與存活時間之影響。現今研究中，結果我們發現大鼠熱中風生成後呈現低腦血流、高血漿濃度TNF-α、低動脈壓、腦缺血及損傷情形，最後導致存活時間縮短。我們嘗試以BQ 788 立即與事先投予大鼠，期望可改善熱中風所致低動脈壓、腦缺血及損傷情形，且可延長存活時間。然而，B受體拮抗劑給予似乎並無法有效的減輕或改善熱中風傷害。而我們目前的研究結果發現，針對大鼠熱中風的動物模式，不管急性或預先投予大鼠內皮素B 受體拮抗劑皆無法有效的減輕或改善熱中風症狀和病理發展。 |
