醣化終極產物在大鼠心肌細胞(H9c2)中對MEK-ERK訊息路徑影響之研究

糖尿病( diabetes mellitus; DM )為最常見的慢性疾病之一，可能會引起的多種併發症，包括腦血管疾病、心血管疾病、視網膜疾病、腎臟疾病，其中由糖尿病引起的心臟疾病稱為糖尿性心臟病(diabetic cardiomyopathy)。研究發現糖尿病會引發血管硬化、心肌發炎、出現心臟功能異常，最終導致心臟衰竭。臨床追蹤發現糖尿病患有醣化終極產物( advanced glycation end-products; AGEs )累積且和心衰竭( heart failure )有正相關。同時AGEs已被證實所產生的活性氧分子( reactive oxygen species; ROS )會造成內皮細胞損害和血管平滑肌細胞肥大。在MEK基因轉殖鼠身上MEK-ERK大量活化會促使心肌肥厚。因此，本研究探討AGEs處理大鼠心臟細胞( H9c2 )後對細胞肥大的影響，所產生的ROS對於訊息路徑的影響。結果顯示AGEs造成細胞肥大，增加細胞總蛋白質生成量，同時會刺激ROS產生來調控MEK-ERK活化，加入ROS抑制劑( NAC )則可抑制此現象。本論文結果顯示AGEs會造成細胞肥大，並且經由ROS調控MEK-ERK活化。因此，AGEs可能藉由ROS調控MEK - ERK途徑使心臟細胞肥大造成糖尿病性心臟病。

關鍵字

糖尿病；醣化終極產物

並列摘要

One of the common chronic diseases is diabetes mellitus ( DM ), that lead various complications, include cerebrovascular disease, cardiovascular disease, retina diseases and kidney disease. The heart disease complication of diabetes is diabetic cardiomyopathy. The major problem is metabolic abnormalities may cause hardening of the arteries, myocardial inflammation, cardiac function abnormal, and leading to heart failure. In clinical setting, advanced glycation end-products ( AGEs ) accumulation and heart failure are positive correlation in DM patients. Ample evidence has suggested that AGEs accumulation increase reactive oxygen species ( ROS ) production and lead to cardiac hypertrophy. Furthermore, activation of MEK-ERK signaling regulates cardiomyocyte hypertrophy in MEK1 transgenic mice. In this study, we proposed that AGEs correlated with cell hypertrophy and affected on signal transduction pathway. We demonstrated that AGEs induced cell hypertrophy and increased the levels of total protein. Furthermore, ROS production and activation MEK-ERK were increased by AGEs. At the same time, when cell pretreated ROS inhibitor ( NAC ) the activation was blocked. This finding indicated that AGEs play an important role in heart hypertrophy through ROS to activate the MEK-ERK pathway.

並列關鍵字

Diabetes mellitus ； Advanced glycation end products

參考文獻

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國際替代計量

醣化終極產物在大鼠心肌細胞(H9c2)中對MEK-ERK訊息路徑影響之研究

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