- 學位論文
乙醯左旋卡尼汀可改善streptozotocin誘發糖尿病鼠併發之動脈硬化及心室肥厚
Acetyl-l-carnitine attenuates arterial stiffness and cardiac hypertrophy in streptozotocin-induced diabetic rats
摘要
背景：持續存在之高血糖、血脂異常以及左旋卡尼汀 (l-carnitine，LC)缺乏等糖尿病代謝異常病徵會導致細胞內氧化壓力增加進而造成動脈功能發生障礙。乙醯左旋卡尼汀 (acetyl-l-carnitine，ALC)在眾左旋卡尼汀的衍生物中具最佳抗氧化能力而且同樣具有調控脂肪酸代謝的功能。現今雖已證實ALC對於糖尿病之神經病變具有療效,但針對於脈態血行力學方面的作用以及預防糖尿病心血管併發症方面的研究卻仍闕如。因此，本篇研究中以特徵阻抗分析來釐清ALC對於streptozotocin誘發之糖尿病Wistar大鼠動脈管特性的作用，並同時評估ALC對於糖尿病造成脂質過氧化 (lipid peroxidation)增加以及血脂參數異常的影響。 方法：八週大的Wistar-Kyoto大鼠從尾部靜脈注射streptozotocin (STZ，55 mg kg-1) 以誘發糖尿病。兩天後經檢測確定已顯現高血糖病徵並穩定兩週之後,於每日飲用水中餵予ALC (150 mg kg-1) 進行為期八週的療程，並以年齡匹配之糖尿病鼠作為對照組別。 結果：與糖尿病鼠組別相較，經由ALC治療八週後的糖尿病鼠顯示，在總周邊阻力及主動脈特徵阻抗等參數上均無差異。相對的，在經ALC治療後，波傳輸時間 (wave transit time，τ) 明顯增加21.04±0.34 to 24.23±0.55 ms (P<0.001)，且波反射係數大幅降低0.71±0.04 to 0.47±0.03 (P<0.001)。此外，糖尿病中偏高的游離脂肪酸、三酸甘油脂、丙二醛 (malondialdehyde，MDA)血中濃度以及MDA動脈含量,給予ALC治療後有部份回復的現象。顯示ALC可能藉其代謝方面功能與本身之抗氧化能力改善糖尿病所造成動脈系統相關聯之左心室收縮負荷增加。心室重量經體重校正後之比值 (心室肥厚的指標) 亦可經由餵予ALC後減少2.46±0.05 to 2.01±0.04 mg g-1 (P<0.001)。 結論：經過ALC長期治療後，能顯著改善糖尿病所引起之心室負荷狀態以及波傳輸現象惡化情形，推測可能是由於ALC能降低糖尿病中升高的氧化壓力所致。
並列摘要
Background: Persistent hyperglycemia, dyslipidemia and carnitine deficiency contribute to enhanced oxidative stress, which causes arterial dysfunction in diabetes mellitus. Acetyl-l-carnitine (ALC) has the best antioxidant capacity among carnitine derivates and has similar action on fatty acid metabolism. Although ALC has been proven to be beneficial for diabetic neuropathy, little attention has been given to the pulsatile hemodynamic responses to ALC in preventing diabetes-associated vascular complications. Herein, we determined the effects of ALC on physical properties of the arterial system in streptozotocin (STZ)-induced diabetes in Wistar rats, using aortic impedance analysis. In addition, the influences of ALC in diabetes-derived lipid peroxidation and abnormal lipid profiles were also measured. Materials and methods: Diabetes was induced in Wistar-Kyoto rats by a single tail vein injection with STZ (55 mg kg-1). After induction of hyperglycemia and stabilization for 2 weeks, animals were daily treated with ALC (150 mg kg-1 in drinking water) for 8 weeks and compared with the untreated aged-matched diabetic controls. Results: After exposure to ALC, the STZ-diabetic rats showed no alterations in total peripheral resistance and aortic characteristic impedance. In contrast, treatment of this experimental diabetic rats with ALC resulted in a significant rise in wave transit time, from 21.04±0.34 to 24.23±0.55 ms (P<0.001) and a fall in wave reflection factor, from 0.71±0.04 to 0.47±0.03 (P<0.001). Moreover, rising circulating NEFA and triglycerides concentration and increasing malondialdehyde (MDA) content in plasma and aortas of diabetes rats were decreased in ALC treatment group. These suggested that ALC might attenuate the diabetes-derived augmentation in systolic load of left ventricular coupled to its arterial system possibly correlating with its metabolic and antioxidant property per se. The ratio of left ventricular weight to body weight, an indicator of cardiac hypertrophy was also attenuated by the action of ALC in diabetic rats, from 2.46±0.05 to 2.01±0.04 mg g-1 (P<0.001). Conclusions: We conclude that long-term supplementation of ALC to diabetic rats imparts significant protection against the diabetes-related deterioration in ventricular loading conditions and wave reflection phenomena properly via alleviating the increasing oxidative stress in the STZ-induced rats.