熱中風為臨床醫學上一種危急的疾病，主要症狀有高體溫﹑多器官衰竭、中樞神經損傷。有許多證據顯示，睪固酮在很多疾病中扮演主要的危險因子，包括敗血症、休克、創傷等重症。雖然有研究指出，雄性大鼠之睪固酮與調節熱平衡有關，但尚不明瞭於熱中風的疾病模式，是否也扮演主要危險因子？因此，本研究提出「阻斷雄性素作用可以降低熱中風引起的死亡率」假說，藉由去勢手術或雄性素拮抗劑氟他胺藥物來降低雄性素作用，探討對雄性動物的熱耐受性影響。實驗動物為八週齡大的ICR雄性小鼠，隨機分為數組，包括：常溫對照組、去勢小鼠、假手術去勢小鼠、去勢後補充睪固酮小鼠、去勢後假補充睪固酮小鼠、氟他胺前處理小鼠、對照藥物前處理小鼠、氟他胺後處理小鼠、對照藥物後處理小鼠。除了常溫對照組小鼠於室溫環境下未受熱外，其餘小鼠均給予「全身性均勻受熱」的熱中風動物模式，維持在41.2℃的環境1小時，再取出置於室溫環境下，連續觀察四天存活者做為存活率的計算。所有的生理與生化參數均於受熱完成後2.5小時測量。實驗結果顯示：去勢小鼠與氟他胺前處理＆後處理小鼠，均能顯著性 (1) 降低熱中風引起的死亡率與失溫現象，(2) 降低腦神經細胞損傷，(3) 減少下視丘，脾臟，肝臟，腎臟的細胞凋亡現象；而去勢後補充睪固酮小鼠，則會降低上述的保護性效果。此外，氟他胺治療小鼠亦能顯著性降低血液中與熱中風相關的損傷因子，如：氧自由基、乳酸去氫酶、TNF-α、IL-6、骨髓過氧化酶活性。綜合上述結論：阻斷雄性素作用可以保護因熱中風引起的腦神經細胞損傷、多重器官衰竭與致命性傷害。

Heatstroke is a lethal disease characterized by hyperpyrexia, multiple organ failure, and predominant central nervous system dysfunction. Many evidences showed that testosterone has been implicated as a significant risk factor for many diseases such as sepsis, strokes and severe injury. Although it has shown that testosterone plays a role in the regulation of heat balance in male rats, it remains unknown whether it also plays a significant risk factor in the heatstroke model. The hypothesis was proposed that androgen blockade can attenuate the heatstroke-induced mortality. The androgen effect was inhibited by surgical castration or androgen antagonist (flutamide) to investigate the heat tolerance of male animals. The experimental animals were ICR male mice of 8-wk-old. The animals were randomly divided into several groups. It included the normothermic controls, castrated mice and sham-castrated mice, castrated mice with testosterone replacement and castrated mice with vehicle replacement, flutamide pre-treated mice and vehicle pre-treated mice, flutamide post-treated mice and vehicle post-treated mice. The normothermic controls of mice were exposed to room temperature. Other groups were all subjected to the animal heatstroke model of whole body hyperthermia (WBH) at 41.2℃ for 1 hour and then allowed to recover at room temperature. Mice that survived on day 4 of WBH were considered survivors. Physiological and biochemical parameters were monitored 2.5 h after WBH. The main results showed that castration and flutamide pre-treated or post-treated mice all significantly (i) attenuated heatstroke-induced mortality and hypothermia, (ii) diminished the neuronal damage of brain, (iii) reduced the numbers of the apoptotic cells in the hypothalamus, the spleen, the liver, and the kidney. The above protective effects of castrated mice were prevented by testosterone replacement. In addition, flutamide therapy mice also significantly attenuated the heatstroke-related damage factors in plasma such as oxidative free radicals, lactate dehydrogenase, TNF-α, IL-6, myeloperoxidase activity. In conclusion, the androgen blockade can protect the male mice from heatstroke-induced neuronal damage of brain, multiple organ degeneration and lethality.

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