腺病毒介導胸苷激酶基因對靜脈平滑肌細胞增殖及內膜增生抑制作用的研究_《中國普外基礎與臨床雜志》

作者：

羅濤 ¹ , 張強 ² , 張建 ¹ , 李建新 ¹ , 谷涌泉 ¹ , 俞恒錫 ¹ , 汪忠鎬 ¹

1.首都醫科大學血管外科研究所、首都醫科大學宣武醫院血管外科（北京100053）;;
2.中國醫科大學附屬第一臨床醫院血管外科(沈陽110001);

關鍵詞：

內膜增生基因治療移植靜脈胸苷激酶基因

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目的探討以腺病毒為載體介導胸苷激酶（tk）基因對靜脈平滑肌細胞增殖及內膜增生的抑制作用。
方法腺病毒載體攜tk及β半乳糖苷酶（lacZ）基因轉染人的大隱靜脈平滑肌細胞及大隱靜脈片,以不同濃度的更昔洛韋（GCV）培養。通過Xgal染色觀察標記基因lacZ的表達效率。將轉染tk基因陽性與tk基因陰性的平滑肌細胞以不同的比例混合培養觀察旁觀者效應。將轉染tk基因的靜脈片在含有GCV的培養液中培養14 d，取標本進行HE、VG染色，輔以計算機圖像分析，觀察內膜增生情況。
結果腺病毒載體能有效地轉染培養的平滑肌細胞和靜脈片中的平滑肌細胞，外源基因表達持續14 d。平滑肌細胞增殖受抑制程度與GCV的濃度和tk表達的水平呈正相關。轉染lacZ的平滑肌細胞則不被GCV抑制。混合細胞培養（tk陽性及tk陰性細胞混合），當10%的細胞表達tk基因時，細胞生存率下降了55%。在靜脈片培養實驗中，tk/GCV組與對照組（lacZ/GCV和tk/GCV-）比較，前者內膜增生60%受到抑制。
結論tk基因合并GCV治療具有抑制平滑肌細胞增殖和移植靜脈內膜增生的作用, tk基因治療具有旁觀者效應。

引用本文： 羅濤,張強,張建,李建新,谷涌泉,俞恒錫,汪忠鎬. 腺病毒介導胸苷激酶基因對靜脈平滑肌細胞增殖及內膜增生抑制作用的研究. 中國普外基礎與臨床雜志, 2006, 13(3): 291-294. doi: 復制

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10.	Robe PA, Jolois O, N’Guyen M, et al. Modulation of the HSVTK/ganciclovir bystander effect by nbutyrate in glioblastoma: correlation with gapjunction intercellular communication [Ｊ]. Int J Oncol， 2004; 25(1)∶187.
11.	Soyombo AA, Angelini GD, Bryan AJ, et al. Intimal proliferation in an organ culture of human saphenous vein [Ｊ]. Am J Pathol， 1990; 137(6)∶1401.
12.	Ojha M. Wall shear stress temporal gradient and anastomotic intimal hyperplasia [Ｊ]. Circ Res， 1994; 74(6)∶1227.

1. Davies MG, Hagen PO. Pathophysiology of vein graft failure: a review [Ｊ]. Eur J Vasc Endovasc Surg， 1995; 9(1)∶7.
2. Ip JH, Fuster V, Badimon L, et al. Syndromes of accelerated atherosclerosis: role of vascular injury and smooth muscle cell proliferation [Ｊ]. J Am Coll Cardiol， 1990; 15(7)∶1667.
3. Bulkley BH, Hutchins GM. Accelerated “atherosclerosis”. A morphologic study of 97 saphenous vein coronary artery bypass grafts [Ｊ]. Circulation， 1977; 55(1)∶163.
4. Guzman RJ, Hirschowitz EA, Brody SL, et al. In vivo suppression of injuryinduced vascular smooth muscle cell accumulation using adenovirusmediated transfer of the herpes simplex virus thymidine kinase gene [Ｊ]. Proc Natl Acad Sci USA， 1994; 91(22)∶10732.
5. 羅濤，張強，刁彥鵬，等. 腺病毒載體轉染人大隱靜脈平滑肌細胞效率的研究 [Ｊ]. 中華實驗外科雜志, 2003； 20（3）∶209.
6. Francis SC, Raizada MK, Mangi AA, et al. Genetic targeting for cardiovascular therapeutics: are we near the summit or just beginning the climb? [Ｊ]. Physiol Genomics, 2001; 7(2)∶79.
7. van Dillen IJ, Mulder NH, Vaalburg W, et al. Influence of the bystander effect on HSVtk/GCV gene therapy. A review [Ｊ]. Curr Gene Ther, 2002; 2(3)∶307.
8. Channon KM, Fulton GJ, Gray JL, et al. Efficient adenoviral gene transfer to early venous bypass grafts: comparison with native vessels [Ｊ]. Cardiovasc Res， 1997; 35(3)∶505.
9. Borrelli E, Heyman R, Hsi M, et al. Targeting of an inducible toxic phenotype in animal cells [Ｊ]. Proc Natl Acad Sci USA， 1988; 85(20)∶7572.
10. Robe PA, Jolois O, N’Guyen M, et al. Modulation of the HSVTK/ganciclovir bystander effect by nbutyrate in glioblastoma: correlation with gapjunction intercellular communication [Ｊ]. Int J Oncol， 2004; 25(1)∶187.
11. Soyombo AA, Angelini GD, Bryan AJ, et al. Intimal proliferation in an organ culture of human saphenous vein [Ｊ]. Am J Pathol， 1990; 137(6)∶1401.
12. Ojha M. Wall shear stress temporal gradient and anastomotic intimal hyperplasia [Ｊ]. Circ Res， 1994; 74(6)∶1227.

《中國普外基礎與臨床雜志》

腺病毒介導胸苷激酶基因對靜脈平滑肌細胞增殖及內膜增生抑制作用的研究

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《中國普外基礎與臨床雜志》

腺病毒介導胸苷激酶基因對靜脈平滑肌細胞增殖及內膜增生抑制作用的研究

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

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