有許多文獻指出腺核苷同半胱胺酸(SAH)可能參與心血管疾病與神經損傷疾病的病理作用。熱中風好發於高溫環境下的工作者，會造成高溫、腦缺血、神經異常等情形，而造成多重器官衰竭，最終導致神經細胞損傷或死亡。心血管疾病病理作用與熱中風損傷可能的作用機制類似，並且有文獻指出，心血管疾病患者較正常人易罹患熱中風。然而卻鮮少有研究探討血漿中SAH濃度與熱中風的相關性，血中高濃度SAH是否也可能是熱中風的危險因子。本實驗主要藉由大鼠熱中風動物模式來探討高濃度的SAH是否影響熱中風的生成或加重其損傷程度，以模擬正常人與血漿中含有高濃度SAH的患者罹患熱中風的危險率是否有所差異。大鼠麻醉後，在開始加熱之加熱點靜脈注射高濃度2ml SAH (5 mg/ml in 5 DMSO)或2 ml 5 DMSO後，給予42℃高溫誘發大鼠熱中風生成，再連續記錄大鼠生理參數並觀察影響情況。結果顯示出，加熱點給予前處理高濃度的SAH會縮短熱中風生成時間；大鼠平均動脈壓(MAP)、心跳速率(HR)、直腸溫度(Tco)及腦血流量(CBF)隨著誘發時間的增加而顯著升高，而在SAH加藥組於熱中風所引發缺血、缺氧及神經損傷情況也顯著提前表現。在熱中風生成過程中，觀察加熱點前處理給予高濃度SAH對大鼠體內自由基與細胞介質素的影響，結果發現，給予高濃度前處理SAH的熱中風大鼠會提早表現出血漿中高濃度自由基與細胞介質素的情形，同時也伴隨有組織DNA傷害。根據以上實驗結果推論，動物體血漿中含有高濃度的SAH確實可能成為熱中風生成的高危險因子，而使動物體較易被誘發生成熱中風，同時也會提前表現出熱中風導致的傷害。 Many studies indicated that plasma high levels of S-adenosylhomocysteine (SAH) might be mediated in neuronal injury or death, and it could be also one of the high risk factor in cardiovascular disease. Workers in high temperature and humidity were easy to induce heatstroke formation. Studies found that the heatstroke patients and animals all displayed the central ischemia, hypoxia, neuronal damage, and high mortality. Many literatures suggested that the patients of cardiovascular diseases might be easier to evoke heatstroke induction. However, there is less attention to investigate what role of the SAH played during heatstroke induction, and whether plasma high levels of SAH could be also one of high risk factor in heatstroke induction. So far, there is no one strategy can be to tall therapy the heatstroke- induced damage. Consequently, it seems more important to prevent the heatstroke induction. The main purpose of this study is to observe the effects of pretreatment with SAH on heatstroke induction and heatstroke- induced damage by a rat model. Rats under anesthesia were exposed to an ambient temperature (42℃) to induced heatstroke. We observe effects of pretreatment with high concentration 2 ml SAH (5 mg/ml in 5 DMSO) or 2 ml 5 DMSO on heatstroke. Our results showed that rats with high concentration SAH treatment were significantly shrunk the duration time of heatstroke induction. The situations of heatstroke- induced cerebral ischemia, hypoxia and neuronal damage were apparently revealed ahead of time in rats with SAH pretreatment group. During heatstroke induction, we also observe the effects of pretreatment with high concentration SAH on levels of free radicals and cytokines in rats. The similar results were also obtained, the plasma levels of free radicals and cytokines were significantly expressed in advance in rats of high concentration SAH group. Meanwhile, the DNA damage of tissue was also obtained ahead of time in high concentration SAH treatment rats during heatstroke. According to our results, we speculated that animals with high levels of SAH pretreatment may probably be one of high risk factors to early induce heatstroke formation, and beforehand reveal or aggravate the heatstroke- induced damage.
