| 摘要: | 在糖尿病病人身上可以發現到，當處於在一個缺氧的環境下其呼吸反應會相較一般人來的遲鈍，但是其中的機轉並未讓人所明白。在其他的研究指出，糖尿病病人體內的神經調節物質會受到改變或損傷，而在呼吸反應調控方面會因抑制性或興奮性的神經傳導物質影響而有所不同。本研究的目的是在於探討當神經傳導物質- gamma-aminobutyric acid A (GABAA) 和N-methyl-D-aspartic acid (NMDA)的改變而使得糖尿病病人在急性缺氧時的呼吸反應改變。實驗1, 實驗為兩組老鼠，一組為正常另一組使用streptozotocin(STZ, 65 mg/kg i.p.)誘發成胰島素依賴型糖尿病，接給注射DMSO和 bicuculline (0.5 ml/kg s.q.)，利用BUXCO系統給予一般空氣（２１％ Ｏ２）３０分鐘和缺氧氣體（１０％ Ｏ２）３０分鐘接著再給一般空氣(21 %Ｏ２) 10 分鐘和高二氧化碳氣體(8% CO2)20分鐘並給予記錄。實驗2, 同樣為兩組8周大的老鼠,一組是正常狀態下而另一組是使用streptozotocin (STZ, 65 mg/kg i.p.)誘導為胰島素依賴型糖尿病模式，分別給予注射saline 和dextromethorphan (DxM, 0.5 ml/kg s.q.)， 同樣是利用BUXCO系統給予一般空氣（２１％ Ｏ２）３０分鐘和缺氧氣體（１０％ Ｏ２）３０分鐘接著再給一般空氣(21 %Ｏ２) 10 分鐘和高二氧化碳氣體(8% CO2)20分鐘同樣給予記錄。實驗1,結果發現糖尿病組在急性缺氧時的呼吸反應明顯較正常組來的遲鈍。在糖尿病組中給予bicuculline 的介入後其呼吸反應有顯著的恢復，而在正常組的老鼠給予bicuculline 後沒有任何的改變。此實驗結果顯示當ＧＡＢＡＡ接受器被阻斷後糖尿病病人在急性呼吸反應有恢復的現象，顯示其呼吸反應遲鈍是因內因性ＧＡＢＡ的作用特別是對ＧＡＢＡＡ接受器。ＧＡＢＡ調節的改變會損害糖尿病病人在面對睡眠呼吸中止症相關的代償反應。實驗2,結果發現在糖尿病組在急性缺氧時的呼吸反應明顯較正常組來的鈍。在糖尿病組中給予dextromethorphan的介入後其呼吸反應並無顯著差異，在正常組的老鼠予dextromethorphan介入後沒有任何的改變。
Diabetes mellitus (DM) patients exhibit blunted ventilatory responses to acute hypoxia whereas the underlying mechanism is unknown. The purpose of the study is to determine whether altered gamma-aminobutyric acid (GABA)ergic mechanisms acting in GABAA receptors contribute to the abnormal ventilatory response to hypoxia in diabetes mellitus. Ventilatory function ventilation (VE), tidal volume (VT), and breathing frequency (f) was assessed using in an unrestricted whole body plethysmograph (Buxco System) in eight non-DM Wistar rats and 8 streptozotocin(STZ)-induced diabetic rats (65 mg/kg i.p., DM). Part 1, Ventilation (VE), tidal volume (VT), and breathing frequency (f) during room air breathing and in response to acute (<10 min) and sustained (10-30 min) hypoxic (10% O2) and hypercapnia (CO2) challenges were measured on two separate occasions following the randomized blinded administration of equal volumes of DMSO (vehicle), bicuculline (0.5 mg/kg, GABAA receptor antagonist). Part 2, Ventilation (VE), tidal volume (VT), and breathing frequency (f) during room air breathing and in response to acute (<10 min) and sustained (10-30 min) hypoxic (10% O2) and hypercapnia (8% CO2) challenges were measured on two separate occasions following the randomized blinded administration of equal volumes of saline (vehicle) and dextromethorphan (DxM, 0.5 mg/kg, NMDA receptor antagonist).
Part 1, Ventilatory response to acute (not sustained) hypoxia in DM group was significantly (P<0.05) blunted compared to non-DM group. Bicuculline administration in non-DM Wistar rats had no effect on ventilation either during room air breathing, or acute and sustained exposure to hypoxia. In contrast, bicuculline administration in DM group significantly increased ventilatory response to acute hypoxia. However, bicuculline administration in DM Wistar rats had no effect on ventilation either during room air breathing or sustained hypoxia. Blunted ventilatory responses to acute hypoxia in diabetes mellitus appeared to be suppressed by endogenous GABA by acting specifically on GABAA receptors. Altered GABAergic modulation of acute ventilatory response in diabetes might potentially impact sleep apnea episode (acute hypoxia) related ventilatory compensation. Part 2, Ventilatory response to hypoxia in DM group was significantly blunted compared to non-DM group. Dextromethorphan administration in non-DM Wistar rats had no effect on ventilation either during room air breathing, or acute and sustained exposure to hypoxia. In contrast, dextromethorphan administration in DM Wistar rats had no effect on ventilation either during room air breathing or acute and sustained hypoxia. In hypercapnia, to compare vehicles and drugs it no effect on ventilation for either DM and non DM group. |
