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Effects of Specific Endothelin-1 Receptor Antagonists on Proliferation and Fibronectin Production of Glomerular Mesangial Cells Stimulated with Angiotensin Ⅱ

內皮素-1抗體拮抗劑對第二型血管收縮素所誘發之腎絲球間質細胞增生及纖維蛋白元產量之影響

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摘要


第二型血管收縮素(以下簡稱Ang-Ⅱ)是一種極強的血管收縮物質,與腎絲球硬化關係密切。最近的研究顯示Ang-Ⅱ會影響內皮素-1(以下簡稱ET-1),因此本研究之目的即探討ET-1抗體拮抗劑對Ang-Ⅱ所誘發之腎絲球間質細胞增生及纖維蛋白元產量之影響。研究結果:(1)Ang-Ⅱ可誘發腎絲球間質細胞產製較多量之ET-1,thymidine攝取量,細胞數目,及纖維蛋白元產量;(2)基礎thymidine攝取量,細胞數目,及纖維蛋白元產量均可受ET-1之A型抗體拮抗劑部分抑制,但不被ET-1之B型抗體拮抗劑抑制;(3)Ang-Ⅱ所增加之腎絲球間質細胞數目可受ET-1之A型抗體拮抗劑部分抑制,但不被ET-1之B型抗體拮抗劑抑制;(4)Ang-Ⅱ所增加之腎絲球間質細胞纖維蛋白元產量分別可受ET-1之A型及B型抗體拮抗劑部分抑制。本研究結果顯示Ang-Ⅱ可明顯刺激腎絲球間質細胞之細胞增生及纖維蛋白元之產生,且此作用主要可受ET-1之A型抗體拮抗劑部分抑制。

並列摘要


Angiotensin Ⅱ (Ang-Ⅱ) is a potent vasoactive hormone, which plays an important role in the pathogenesis of glomerulosclerosis. Ang-Ⅱ activates many cytokine systems in the kidney. Recent studies indicate that Ang-Ⅱ is closely related to the activation of the endothelin-1 (ET-1) system. The present study was designed to measure the [H^3]-thymidine uptake and fibronectin production of cultured rat mesangial cells stimulated with Ang-Ⅱ, and to evaluate the effects of specific ET-1 receptor antagonists, BQ123 (type A receptor antagonist) and IRL1038 (type B receptor antagonist) on the cells. ET-1 was measured by radioimmunoassay and fibronectin by Western blot analysis. The results were as follows: (1) Ang-Ⅱ enhanced ET-1 production, [H^3]-thymidine uptake, number of cells, and fibronectin production of mesangial cells; (2) all the baseline [H^3]-thymidine uptake, number of cells, and fibronectin production of mesangial cells can be partly suppressed by BQ123, but not by IRL1038; (3) the increment of Ang-Ⅱ-enhanced number of cells can be partly suppressed by BQ123, but not by IRL1038; and (4) the increment of Ang-Ⅱ-enhanced fibronectin production can be partly suppressed by both BQ123 and IRL1038. Our results indicate that Ang-Ⅱ is an active stimulant for the proliferation and fibronectin production of mesangial cells, and the effect is partly suppressed mainly by ET-1 type A receptor antagonists.

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