1-脫氧野尻黴素抑制高糖誘導血管平滑肌細胞位移之作用

The inhibition of 1-Deoxynojirimycin hydrochloride (DNJ) on high glucose induces migration in vascular smooth muscle cell

張雯鈞(Wen-Chun Chang)

指導教授 ： 王朝鐘

中山醫學大學/醫學院/生化暨生物科技研究所/碩士(2012年)

摘要

糖尿病易產生心臟病、腦血管疾病和腎臟病等併發症，皆位居國人十大死因的前十名，這表示糖尿病已不只是單一性的疾病。根據流行病學的調查報告指出，糖尿病病人罹患心血管疾病是非糖尿病患者的四倍；糖尿病病人會因為氧化壓力的增加，或血管內皮的損傷，形成斑塊堆積在血管內，也刺激了血管平滑肌細胞的增生。血管平滑肌的增生與位移與在血管受損及粥狀動脈發展中扮演一個重要的角色。α-glucosidase inhibitor為糖尿病的臨床治療藥物之一，這種藥物會在小腸內阻斷醣類的吸收，達到抑制血糖上升的目的；桑葉萃取物中的 1-Deoxynojirimycin hydrochloride (DNJ) 即為α-glucosidase inhibitor。之前的研究已經證明桑葉萃取物MLE可以抑制血管平滑肌的增生與位移，本論文想更進一步探討桑葉萃取物（Mulberry leaf extract，MLE）抑制血管平滑肌的位移，是否透過MLE中的DNJ ；本研究中利用大鼠的血管平滑肌細胞（Vascular smooth muscle cells，VSMC）A7r5以高糖（25 mM）誘導VSMC增生與位移後再加入不同濃度的DNJ，結果發現DNJ會抑制脂質代謝蛋白FASN和AMPK表現；抑制PI3k/Akt路徑及small G proteins；也會透過抑制AP-1轉錄因子相關蛋白c-Fos、c-Jun的表現，進而抑制MMP-2和MMP-9。此研究證實桑葉萃取物中的成份DNJ可以抑制血管平滑肌細胞的位移。

關鍵字

糖尿病 ； 血管平滑肌細胞 ； 位移 ； 1-脫氧野尻黴素

並列摘要

Diabetes mellitus is the fifth leading cause of death in Taiwan. It has many complications including heart disease, cerebrovascular disease and kidney disease, indicating that it`s not a single disease. Epidemiological survey reports that diabetic mellitus patients with cardiovascular disease are four times higher than non-diabetes mellitus patients. It is because oxidative stress and vascular endothelial injury were increased and plaques were accumulated within the blood vessels in diabetic mellitus patients. Finally, proliferation of VSMC was occurred. These processes were associated with development of atherosclerosis including proliferation and migration of VSMC. Alpha-glucosidase inhibitor is one of the drugs for treatment of diabetes mellitus, which can block the absorption of carbohydrate in the small intestine and achieve the purpose of inhibition of blood sugar levels. The 1-deoxynojirimycin hydrochloride (DNJ), is one component of mulberry leaf extract (MLE), which is an alpha-glucodidase inhibitor. Previous studies have demonstrated that MLE can inhibit proliferation and migration of vascular smooth muscle cells (VSMC). In this study, we further explore that the mechanism of DNJ (one component of MLE) in VSMC. Treatment of vascular smooth muscle cells, A7r5 with different concentration of DNJ and sugar (25 mM), MTT assay was performed. We found that DNJ could inhibit migration of A7r5 cells by down regulation of Ras/PI3K/Akt signaling and small G protein, AP-1, c-Fos (transcription factor related protein), and c-Jun. Furthermore, our results showed that the lipid metabolism associated proteins FASN and AMPK were regulated by DNJ. This finding indicated that DNJ (the component of mulberry extract) could inhibit migration of VSMC.

並列關鍵字

Diabetes ； Vascular smooth muscle cells ； migration ； 1-DNJ

參考文獻

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