| 摘要: | 血管平滑肌過度表現MMP-2 及 MMP-9蛋白質以及平滑肌細胞的轉移被認為與動脈粥樣化的病程發展有密切關聯。MMP-2 及 MMP-9的蛋白質由許多的調節路徑所調控，如nuclear factor kappa (NF-κB)，p38 mitogen activated protein kinase (MAPK)，extracellular signal regulated kinase 1 & 2 (ERK 1/2)，及 Akt。Di(2-ethylhexyl) phthalate (DEHP)是常見的一種塑化劑，近年來被發現與動脈粥樣化的發生或發展有相關性，其機轉可能包括增加血管平滑肌的MMP-2及MMP-9蛋白質表現有關。研究發現蛹蟲草萃出物可以預防高血脂症，然而蛹蟲草萃出物對於DEHP-誘發動脈粥樣化的保護機制從未被揭露過。血管平滑肌以5 ppm DEHP及蛹蟲草萃出物(濃度由1-50 μg/ml)作用24小時之後檢視MMP-2及MMP-9蛋白質表現、作用20分鐘之後檢視p38 MAPK、Akt、ERK1/2蛋白質表現、以及12小時之後檢視NF-κB蛋白質表現。結果發現:蛹蟲草萃出物可以有效抑制DEHP 5 ppm刺激的MMP-2及MMP-9蛋白質表現，且為一種濃度依賴性的關係。此外，DEHP-誘導的p38 MAPK、ERK1/2、Akt、以及NF-κB蛋白質表現以及血管平滑肌遷移也受到蛹蟲草萃出物的抑制。總結，蛹蟲草萃出物藉由抑制MMP-2及MMP-9蛋白質表現的調節路徑分子(p38 MAPK、ERK1/2、Akt、以及NF-κB)表現，具有潛在發展成為抑制動脈粥樣化的病程惡化的藥物。
Over-expressions of MMP-2 and MMP-9 and cell migration of vascular smooth muscle cells (VSMC) have been considered as two of several biomarkers in the progression of atherosclerosis. Several signal transduction systems have been linked to control expressions of MMP-2 and MMP-9, among them are nuclear factor kappa (NF-κB), p38 mitogen activated protein kinase (MAPK), extracellular signal regulated kinase 1 & 2 (ERK 1/2), and Akt. Atherosclerosis can be induced by di(2-ethylhexyl) phthalate (DEHP), which is one of the most common compounds used as plasticizers in most of plastic products. The possible mechanisms of DEHP-induced atherosclerosis include increasing MMP-2 and MMP-9 expression and these regulatory pathways in VSMC. Cordyceps militaris extract has been shown its capability to prevent hyperlipidemia. However, its protective mechanisms against DEHP-induced expressions of MMP-2 and MMP-9 were not elucidated previously. vascular smooth muscle cells (VSMC) was treated with 5 ppm DEHP with or without Cordyceps militaris extract (dose between 1-50 μg/ml) for 24h prior to MMP-2 and MMP-9, 20 min prior to AMPK, ERK1/2, and Akt, and 12h prior to NF-kB expressions. DEHP-induced MMP-2 and MMP-9 expressions were prevented by treatment of Cordyceps militaris extract in a dose dependent manner. In addition, DEHP-induced phosphorylated MAPK, ERK1/2, Akt, and NF-κB expressions and VSMC migration were also inhibited by Cordyceps militaris extract treatment. In conclusion, Cordyceps militaris extract may have potential role in preventing DEHP-induced atherosclerosis progression by inhibiting MMP-2 and MMP-9 expressions via MAPK, ERK1/2, Art, and NF-κB pathways. |
