| 摘要: | 本研究目的為探討丹參乙醇粗抽物(SMEtOH)及其活性成分丹參酮 IIA (TS IIA)之抗焦慮作用。實驗以舉臂型十字迷宮(EPM)及探洞實驗(Hole-board test)誘發動物焦慮模式評估SMEtOH及其活性成分TS IIA之抗焦慮作用。並分別於併用影響中樞GABAergic及serotonergic system之藥物後，進行舉臂型十字迷宮實驗及測定小鼠腦皮質、海馬迴與紋狀體組織中神經傳導物質血清素(5-HT)、正腎上腺素(NE)、多巴胺(DA)及其代謝物的濃度以探討TS IIA抗焦慮作用之機轉。
結果顯示，口服SMEtOH (100, 500 mg/kg)及腹腔注射TS IIA(6, 30 mg/kg)一次給藥後，對小鼠在舉臂型十字迷宮之開放臂的滯留時間及進入次數有增加的作用，減少小鼠在封閉臂之滯留時間及進入次數。又於探洞實驗中，能增加探洞次數及持續時間。於自發運動量實驗中，SMEtOH (500 mg/kg)及TS IIA(30 mg/kg )會降低小鼠水平移動距離及增加休息的時間。
在高效液相層析儀分析小鼠腦內單胺及代謝物濃度的實驗中發現，TS IIA(6 mg/kg)能減少小鼠腦中皮質與海馬迴組織組織中5-HT、NE及DA的濃度及增加代謝物5-HIAA、MHPG及DOPAC的濃度，對紋狀體組織內DA與DOPAC濃度則無影響。另外，TS IIA (30 mg/kg)能減少小鼠腦中皮質、海馬迴與紋狀體組織中5-HT、NE及DA的濃度及增加代謝物5-HIAA、MHPG及DOPAC的濃度。而TS IIA亦能增強Diazepam (GABA receptor agonist)與Buspirone (somatodendritic 5-HT1A partial agonist)、P-MPPI (5-HT1A selective antagonist)、RIT (5-HT2 selective antagonist)之抗焦慮作用，並拮抗WAY-100635 (somatodendritic 5-HT1A selective antagonist)、8-OH DPAT (5-HT1A selective agonist)、DOI (5-HT2 selective agonist)誘發之焦慮作用。
綜合以上結果，顯示SMEtOH與TS IIA在舉臂型十字迷宮與探洞實驗誘發小鼠焦慮模式中，均具有明顯之抗焦慮作用。TS IIA之抗焦慮機轉可能與活化GABA receptor和突觸前5-HT1A autoreceptor及降低突觸後5-HT1和5-HT2 receptor的活性，並減少皮質、海馬迴與紋狀體組織中5-HT、NE及DA的釋放有關。
The anxiolytic effect of ethanol extract of Salvia miltiorrhiza Bunge (SMEtOH) and tanshinone IIA (TS IIA) in mice were investigated by using elevated plus-maze (EPM) and the hole-board test. The locomotor activity was examined using the open-field test. In addition, the anxiolytic-like mechanisms of tanshinone IIA were examined by combining with GABAergic and serotonergic agents, and measuring the levels of monoamines and its metabolites in cortex, hippocampus and striatum of mice.
The results shown that SMEtOH (100, 500 mg/kg; p.o.) and tanshinone IIA (6, 30 mg/kg; i.p.) increased the time spent and the arm entries in the open arms, and decreased the time spent and the arm entries in the closed arms. SMEtOH (100, 500 mg/kg; p.o.) and tanshinone IIA (6, 30 mg/kg; i.p.) also increased head-dip counts and duration time in Hole-board test. SMEtOH 500 mg/kg and tanshinone IIA 30 mg/kg decreased locomotor activity in the open- field test.
Furthermore, tanshinone IIA at 6 mg/kg decreased the levels of 5-HT, NE and DA, and increased the levels of 5-HIAA, MHPG, DOPAC in the cortex and hippocampus. At 30 mg/kg, tanshinone IIA decreased the levels of 5-HT, NE and DA, and increased the levels of 5-HIAA, MHPG, DOPAC in the cortex, hippocampus and striatum. TS IIA also attenuated the anxiogenic effect of WAY-100635, 8-OHDPAT and DOI and enhanced the anxiolytic effect of BUS, p-MPPI and RIT in the elevated plus-maze.
These results suggested that SMEtOH and tanshinone IIA possessed a significant anxiolytic-like effect. The anxiolytic-like mechanisms of tanshinone IIA may be due to decreasing the levels of 5-HT, NE and DA, and increasing the levels of 5-HIAA, MHPG, DOPAC in the cortex, hippocampus and striatum by activating GABA receptor, pre-synapse 5-HT1A autoreceptor, and inhibiting postsynaptic 5-HT1A and 5-HT2 receptors. |
