Platonin抑制大鼠血管平滑肌細胞增生之機轉探討

血管平滑肌細胞的不正常增生，會造成血管內膜的異常增厚，在很多心血管疾病，例如粥狀動脈硬化及血管再窄化的病程中都扮演了相當重要的角色。本篇論文在探討感光性花青素染劑的platonin (4,4',4''-Trimethyl-3,3',3''-Trihepthyl-7-(2''-thiazolyl)-2,2',-Trimethine Thiazolocyanine-3,3''-Diiodide)抑制大鼠血管平滑肌細胞增生的藥理機轉。經由MTT assay的結果，發現platonin (0.5、1、2與5 microM)以濃度相關性的抑制PDGF-BB誘導血管平滑肌細胞的增生。而在顯微鏡下觀察細胞的型態，則發現有細胞皺縮及凋亡小體(apoptotic body)的產生。以流式細胞儀偵測platonin對細胞週期的影響，發現藥物會使sub G1期增加。因此我們推測platonin除了抑制血管平滑肌細胞的增生作用外,還有可能促使血管平滑肌細胞產生凋亡的情形。接著探討platonin抑制PDGF-BB誘導血管平滑肌細胞增生的機轉。發現platonin並不會影響AKT、ERK的磷酸化，但是有意義的抑制p38及JNK的磷酸化。接續的研究會朝platonin對細胞週期之其它因子及細胞凋亡的影響探討。platonin在免疫調節方面的效果已被證實，本實驗又闡明了有抑制血管平滑肌細胞增生的作用，同樣是抑制細胞增生，接下來的研究可以朝向抑制血管內層新生、治療血管再阻塞或抗癌方面加以發展，相信也是具有潛力的藥物。

關鍵字

血管平滑肌細胞?生； platonin

並列摘要

Abnormal proliferation of vascular smooth muscle cells (VSMCs) results in neointima plays an important role in many coronary diseases including atherosclerosis and restenosis. This research has shown the inhibitory mechanisms of platonin (4,4',4''-Trimethyl-3,3',3''-Trihepthyl-7-(2''-thiazolyl)-2,2',-Trimethine Thiazolocyanine-3,3''-Diiodide) on VSMCs proliferation. By MTT assay, we found that platonin inhibited PDGF-BB-induced vascular smooth muscle cells proliferation in a concentration dependent manner. Then we observed the morphological changes of VSMCs by microscopy. VSMCs were shrinked and apoptotic body were formed. Using flow cytometry, we find that platonin increased the sub-G1 phase of the cell cycle. Thus, we propose that platonin may inhibit PDGF-BB-induced vascular smooth muscle cells proliferation and even increase the apoptosis of VSMCs. And then we investigated the mechanism of platonin inhibiting PDGF-BB-induced vascular smooth muscle cells proliferation. We found that platonin did not inhibit the phosphorylation of Akt and ERK, however platonin could inhibit the phosphorylation of p38 and JNK significantly. JNK inhibition may play an important role in this mechanism according to c-jun inhibition of platonin. We will further focus on investigating the effects of platonin on molecular regulation of cell cycle and apoptosis. In addition to its anti-inflammatory and anti-oxidation activities, this research showed that platonin inhibited VSMCs proliferation. Because of the anti-proliferation effect of platonin, the further efforts to evaluate if platonin exhibits anti-neointimal formation and anti-restenosis effect.

並列關鍵字

vascular smooth muscle cell proliferation ； platonin

參考文獻

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Platonin抑制大鼠血管平滑肌細胞增生之機轉探討

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