| Abstract: | 研究目的：本研究旨在探討慢性濫用甲基安非他命、古柯鹼是否會增加心臟第一型(依靠FAS)、第二型(依靠線粒體)的細胞凋亡途徑。
研究方法及資料：三十二隻雄性三至四個月的Wistar鼠、隨機分配至對照組(佐藥[磷酸鹽緩衝液]，每天皮下注射零點五公撮)；實驗組一(甲基安非他命，每天每公斤皮下注射十毫克)，實驗組二(古柯鹼，每天每公斤皮下注射十毫克)。經過三個月的治療，我們將老鼠切下的左心室，用病理組織學，西方墨點法，DAPI染色，TUNEL檢驗，來檢測心臟的結構及兩種主要的細胞凋亡途徑。
研究結果：和對照組(磷酸鹽緩衝液)比較，實驗組一(甲基安非他命)和實驗組二(古柯鹼)有不正常的心臟結構，擴大的組織間隙，較多的輕微心臟纖維化，較多的TUNEL凋亡細胞。在蛋白質量上，比起對照組(磷酸鹽緩衝液)，實驗組一(甲基安非他命)和實驗組二(古柯鹼)有較高的腫瘤壞死因子-α,Fas 配體,Fas 死亡受體, FADD,活化的caspase-8,和活化的caspase-3(依靠FAS的細胞凋亡)；實驗組一(甲基安非他命) 有較高的Bak, t-Bid, Bak-to-Bcl-xL比率,活性化的caspase-9,和活性化的caspase-3 (依靠線粒體的細胞凋亡)；實驗組二(古柯鹼)有較高的Bax, cytochrome c,t-Bid-to-Bid比率,Bak-to-Bcl-xL比率,Bax-to-Bcl-2 比率,活化的caspase-9,和活化的caspase-3 (依靠線粒體的細胞凋亡)。
結論與建議： 在老鼠的動物實驗上，慢性濫用甲基安非他命、古柯鹼會活化心臟依靠FAS的細胞凋亡途徑(第一型)和依靠線粒體的細胞凋亡途徑(第二型)；是否提供了人類長期使用甲基安非他命、古柯鹼也會造成心臟異常病變的一個可能機轉。
Objective：The purpose of this study is to evaluate whether long-term methamphetamine, cocaine abuse will increase cardiac Fas-dependent (type I) and mitochondria-dependent (type II) apoptotic pathways.
Methods and Materials：Thirty-two male Wistar rats at 3-4 months of age were randomly divided into a vehicle-treated group (phosphate-buffered saline, PBS, 0.5ml, SQ per day), a methamphetamine-treated group (MA, 10mg/kg SQ per day) and a cocaine-treated group (Cocaine, 10mg/Kg, SQ per day). After three months of treatment, the myocardial architecture and two major apoptotic pathways in the excised left ventricles were measured by histopathological analysis, Western blotting, DAPI staining and TUNEL assays.
Results：Abnormal myocardial architecture, enlarged interstitial spaces, more minor cardiac fibrosis and cardiac TUNEL-positive apoptotic cells were observed at greater frequency in the MA group, Cocaine group than the PBS group. Protein levels of TNF-alpha, Fas ligand, Fas death receptor, FADD, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts were significantly increased in the MA group, Cocaine group, compared to the PBS group. Protein levels of cardiac Bak, t-Bid, Bak-to-Bcl-xL ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the MA group; protein levels of cardiac Bax, cytochrome c, t-Bid-to-Bid, Bak-to-Bcl-xL, Bax-to-Bcl-2 ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the Cocaine group; compared to the PBS group.
Conclusion and Suggestion：Chronic methamphetamine, cocaine exposure will activate the cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, which may indicate a possible mechanism for the development of cardiac abnormalities in humans with long-term methamphetamine, cocaine abuse. |
