由本研究的結果數據顯示，熱中風後的大鼠會有循環性休克、減短存 活時間、生理參數異常、下視丘神經細胞凋亡、引發全身性發炎反應等情 形。而第(C)~(E)組的 hUCBCs 實驗組結果也應證了實驗室系列性研究中 所提到的，利用 hUCBCs 治療熱中風大鼠，可延長存活時間、降低循環性 休克反應；(D),(E)組也應證了可減少下視丘細胞凋亡、降低全身性發炎反 應。所以 hUCBCs 確實是可改善熱中風後所產生的併發症。且在(D)組的 連續性植入 hUCBCs 結果可看到，存活時間更長、發炎指數降的更低、下 視丘細胞凋亡數量顯著得到改善，這顯示了連續性植入在未來是可期的一 種新的治療策略。
35
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圖 1. 連續監測平均動脈壓(MAP)、心跳速率(HR)、肛溫(Tco)的生理參數 變化 (N=6)
此為連續監測生理參數統計圖，各組別圖示如粗框內所示。
所有數據均以平均值±標準差表示，實驗動物數目以括號 N 表示(N=6，每組皆為 6 隻)。
(A)NC 組於實驗開始約 480 分鐘(或他組實驗結束後)以過量聚氨酯麻醉犧牲。
*P < 0.05 與 NC 組比較； +P < 0.05 與 S2 組比較；#P < 0.05 與 H+S 組比較
48
圖2. 熱中風後下視丘神經細胞損傷之組織學染色圖(H&E染色) (N=6) (A)常溫控制組(NC)。(B)熱中風控制組(HS+S2)。(C)人類臍帶血幹細胞單劑+生理食鹽 水治療之熱中風組(HS+H+S)。(D)人類臍帶血幹細胞連續兩劑治療之熱中風組(HS+H2)。
49
圖 3-1. TUNEL/DAPI 染色比較大鼠熱中風後下視丘神經細胞凋亡(N=6) (A)常溫控制組(NC)。(B)熱中風控制組(HS+S2)。(C)人類臍帶血幹細胞單劑+生理食 鹽水治療之熱中風組(HS+H+S)。(D)人類臍帶血幹細胞連續兩劑治療之熱中風組 (HS+H2)。綠色螢光點代表 TUNEL 染出的凋亡細胞，藍色螢光點代表 DAPI 染色顯 示的細胞核，Merged 圖系利用影像重疊技術，確認細胞凋亡表現區域。
50
TUNELpostive cells / mm2
0
51
52
53
表 1. 常溫控制組、熱中風控制組、熱中風治療組各實驗組之存活時間表
Treatment group (N=6) Survival time (mins) (A) Normothermic control (NC) >480
(B) HS + Saline + Saline (S2) (0.3ml, 0.3ml, i.v.)
31±3
(C) HS + hUCBCs + Saline (H+S) ( 5X105/0.3ml, 0.3ml, i.v.)
69±8a
(D) HS + hUCBCs + hUCBCs (H2) ( 5X105/0.3ml, 5X105/0.3ml, i.v.)
200±25abc
(E) HS + hUCBCs (H1) ( 1X106/0.3ml, i.v.) 99±7a
除常溫控制組外，熱中風控制組及熱中風治療組之大鼠皆暴露在熱環境(43℃,70分鐘)下 誘導熱中風，之後立即回覆室溫(26℃)並給予各組第一劑的靜脈注射治療，在存活時間 的第12分鐘(B) 、(C) 、(D)給予第二劑靜脈注射治療。所有數據均以平均值±標準差表 示，動物數目以括號N表示(N=6，每組皆為6隻)。第(A)組於實驗開始約480分鐘(或他組 實驗結束後)以過量聚脂胺麻醉犧牲。
aP<0.05 與S2組比較；bP<0.05 與H+S組比較；cP<0.05 與H1組比較。
54
Treatment groups Neuronal
damage score (0-3)
(A) Normothermic controls(NC)
(B) Saline+Saline(S2) --- treated heatstroke rats (C) hUCBCs+Saline(H+S) --- treated heatstroke rats (D) hUCBCs+hUCBCs(H2) --- treated heatstroke rats
0 2a
1ab 1ab
Neuronal damage score 0 Normal = 0%
1 neurons damaged = 30%
2 neurons damaged = 60%
3 neurons damaged = 100%
55
附錄 1. 熱暴露生理機制圖
Epstein Y, Roberts WO. The pathopysiology of heat stroke: an integrative view
of the final common pathway. Scand J Med Sci Sports. 2011; 21:742-748.
56
附錄 2. 熱中風病理生理機制
Bouchama A, Knochel JM. Heat stroke. N Engl J Med. 2002; 346:1978-1988.