洪冠予2006-07-262018-07-112006-07-262018-07-112002http://ntur.lib.ntu.edu.tw//handle/246246/23561腹膜透析(PD)病人的腹膜長期接觸含高糖(high glucose, HG)成分的透析液，會發生 纖維硬化。吾人曾經報告: TGF-b 可以刺激人類腹膜表面細胞(human peritoneal mesothelial cell, HPMC)內纖維蛋白基因[type I collagen, proá1(I)]表現增加，此機轉可能 與活化傳遞路徑ERK 有關，而且可以被dipyridamole 抑制。而HG 也可以刺激HPMC 的proá1(I)表現增加，但是dipyridamole 的效果及機轉仍待釐清。本研究中吾人發現: HG 具有刺激HPMC 中ERK, p38 MAPK 等傳遞路徑活化、增進纖維蛋白基因proá1(I)]表現 的作用。Dipyridamole 可以抑制上述HG 的作用。吾人進一步探究發現: 使用PD98059 或SB203580, 各是ERK 及p38 MAPK 路徑的阻斷劑, 可以成功阻斷HG 之刺激HPMC 內proá1(I)表現增加的作用。暗示: ERK 及p38 MAPK 兩條路徑應該都參與HG 之刺激 HPMC 內proá1(I)表現增加的作用。Dipyridamole 雖然可以抑制ERK 活化，但是卻不會阻止p38 MAPK 之被HG 活化。吾人初步結論是：dipyridamole 的確可以有抑制HG 刺激HPMC 內纖維蛋白基因表 現增加的效果，而此種作用的機轉主要可能予透過抑制HPMC 內ERK1/2 路徑被HG 刺激活化有關。High glucose (HG) contents of dialysate exerts fibrogenic effects on peritoneum of patients on peritoneal dialysis (PD). We previously had found in human peritoneal mesothelial cell (HPMC) that the fibrogenic effect of TGF-ß was mediated via activation of extracellular signal-regulated kinase (ERK) cascade and is suppressed by dipyridamole. However, the molecular mechanisms mediating fibrogenic reactions of HG in HPMC and whether it can be modulated by dipyridamole has never been investigated. HG (25 mM), compared with normal glucose (5.5 mM), significantly activate ERK1/2, p38 MAPK and increased type I pro-collagen [proá1(I)] mRNA level in HPMC. HPMC pre-treated with dipyridamole dose-dependently inhibit effects of HG. HPMC pre-treated with PD98059 and SB203580, which selectively inhibited ERK and p38 MAPK, respectively, prevented HG-induced proá1(I) mRNA upregulation. It implicated that both ERK and p38 MAPK are involved in response to HG. Dipyridamole inhibited the ERK activation, but not the activation of p38 MAPK, of HPMC by HG. We postulated that dipyridamole may inhibit the HG-induced matrix gene expression, thus may have clinical implications as therapeutic agents for prevention of peritoneal fibrosising syndrome (PFS).application/pdf141998 bytesapplication/pdfzh-TW國立臺灣大學醫學院內科腹膜透析dipyridamole高糖纖維蛋白訊息傳遞peritoneal dialysismesothelial cellhigh glucosesignal transductionreporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/23561/1/902314B002272.pdf