- 期刊
Characterization of Therapeutic Approaches in Preventing Balloon Injury-induced Restenosis in Carotid Arteries of Rats
探討氣球擴張所引起血管再阻塞之抑制方法
摘要
背景 平滑肌細胞的增生是導致氣球擴張所引起血管再阻塞的主要原因之一，而在調控這一細胞增生的訊號傳遞路徑中，p21ras被認為是具有決定性的角色。為證實這一假說，我們將一個p21ras的變異基因（RasN17）做入具有高轉殖性的腺病毒中，從而觀察這一基因對於細胞增生的影響。 方法 利用病毒攜帶的lacZ基因感染平滑肌細胞來評估基因轉殖率，再以[3H] thymidine incorporation的方法來測定AdRasN17抑制細胞分裂的能力。在動物質驗方面，利用氣球擴張在大鼠總頸動脈產生血管再阻塞，並同時給予AdRasN17，兩週後取出血管做組織切片分析。 結果 在細胞培養的實驗中我們發現，由腺病毒所引導的基因轉殖率高達95%。在動物實驗中，則發現RasN17有效抑制由氣球擴張所造成大鼠血管新生的內膜層。在分析血管內膜層和中層的比例方面，我們發現以AdLacZ得對照組所測得的比例約為1.96，經RasN17治療的內膜層和中層的比例則降低到0.98。結論 從這一實驗的結果顯示，利用此腺病毒所表達的RasN17，應能有效的降低因氣球擴張所造成血管的再阻塞。
並列摘要
Background: Proliferation of smooth muscle cells has been attributed to balloon injury-induced v;“cular restenosis. It was reported that a very upstream signaling molecule p21ras leading to cellular proliferation may playa critical role in such vascular pathogenesis. To test this hypothesis,we constructed anadenoviral chimera containing a dominant negative mutant of p21ras proteins (AdRasN17) to evaluate their effects on cell proliferation. Method: Transfection efficiency was analyzed using lacZ expression mediated by adenoviral vectors or lipofectamine. The inhibitory effects of AdRasNl7 on smooth muscle cell proliferation were tested using [3H] thymidine incorporation assay. Carotid arteries of rats were balloon injured with concomittant application of AdRasN17 and humanely killed 2 weeks after surgery. The paraffin-embedded cross sections were then st;“ned with hematoxylin and eosin for histological anal ysis. Results: The virus-mediated transfection efficiency was over 95% as demonstrated by lacZ expression when compared with less than 5% of lipofectamine-mediated transfection. The neointima to media ratio from AdLacZ-infected vessels and AdRasN17-infected vessels was 1.96 and 0.98, respectively. Conclusions: The50% reduction in neointimal formation suggests that the virus-mediated gene approach can be an alternative remedy in preventing vascular restenosis caused by balloon injury.
延伸閱讀
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