於最近的許多研究證實了老鼠與人類發生熱中風時有著相同的反應，諸如過高熱、低血壓、肝腎衰竭、血管內凝血病變、全身性發炎、大腦缺血損傷及功能失調。在本系列的研究中，我們嘗試著評估人類臍帶血細胞 (HUCBC)或由其純化出的造血幹細胞(CD34+) 或premarin(為一水溶性共結的雌激素)，是否能藉由改善其多器官功能失調而達到延長其存活的時間或比率。大鼠於麻醉下在熱中風生成時或熱壓力開始前24小時為治療的時間點，基本上分成3大組同時給予佐藥液 (1 mg/kg BW, 經股靜脈) HUCBCs (5×105/ml/kg BW, 經股靜脈) CD34+細胞 (1×105- 5×105/ml/kg BW, 經股靜脈)或premarin (1 mg/ml BW, 經股靜脈)，這些實驗組別的大鼠均暴露在環境溫度為43oC予以誘發熱中風，其他組別大鼠暴露於室溫26oC當作常溫控制組，其中低血壓、肝腎功能衰竭 (以血清中尿素氮、肌肝酸、胱胺酸胺基轉化?、丙胺酸胺基轉化?及鹼性磷酸鹽的上升為佐證)，血管內凝血病變 (以PT、aPTT、D-dimer 的上升及血小板數目及protein C下降為佐證)，活化的發炎反應 (以腫瘤壞死因子的上升為佐證) 及大腦功能失調 (以顱內高壓、低血壓、大腦灌流壓下降及大腦缺血缺氧性損傷為佐證)均被監測，當以佐藥液處置的大鼠進行熱中風實驗時，發現其存活時間為19-23分鐘，而以HUCBCs前處理 (熱壓力前24小時給予)或後處理(熱中風開始時立即給予)，來自人類臍帶血的造血幹細胞或premarin於熱中風發生時給予均有顯著的存活時間延長 (約63-291分鐘)，與常溫控制組相較，所有佐藥液處置的熱中風大鼠均呈現低血壓、肝腎功能衰竭、血管內凝血病變、發炎性反應被激發、及大腦缺血性損傷。然而，無論使用HUCBCs前處理或後處理，甚至以造血幹細胞或premarin予以治療均呈現明顯改善上述的熱中風所誘發的反應。此外，血清中IL-10的濃度及神經膠細胞所衍生的神經親和因子，均在臍帶血幹細胞或premarin的治療後明顯上升。由我們的實驗結果顯示人類臍帶血幹細胞或premarin可被用來當作熱中風所誘發多器官衰竭的預防和治療物質。

Recent researches have documented that rodents share with humans almost the same heatstroke reactions such as hyperpyrexia, hypotension, hepatic and renal failure, hypercoagulable state, systemic inflammation, and cerebral ischemia, injury and dysfunction. In this series, we attempted to assess whether human umbilical cord blood cells (HUCBCs), or human umbilical cord blood-derived CD34+ cells, or Premarin (a water-soluble conjugated estrogen sulfate) improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heat stroke or one day before the start of heat stress, were divided into 3 major groups and given vehicle solution (1 mL/kg body weight, i.v.), HUCBCs (5×105/mL/kg body weight, i.v.), CD34+ cells (1×105-5×105/mL/kg body weight, i.v.), or Premarin (1 mg/mL/kg body weight, i.v.). They were exposed to ambient temperature of 43oC to induce heatstroke. Another group of rats were exposed to room temperature (26oC) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidenced by increased tumor necrosis factor-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, hypotension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the vehicle-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Pretreatment (one day before heat stress) or resuscitation (immediately after the onset of heat stroke) with HUCBCs, CD34+ cells or Premarin significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all vehicle-treated heatstroke rats displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, either pretreatment or therapy using CD34+ cells or Premarin significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of interleukin-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ or Premarin pretreatment of therapy during heatstroke experiments. Our data indicate that human umbilical cord blood-derived CD34+ cells or Premarin can be used as a prophylactic and a therapeutic agent for prevention and repair of multiorgan failure in heatstroke.

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