小干扰 RNA 靶向 c-myc 抑制大鼠静脉移植物模型中的静脉移植物再狭窄。
Small interfering RNA to c-myc inhibits vein graft restenosis in a rat vein graft model.
机构信息
Department of Cardiothoracic Surgery, Jinling Hospital, Clinical Medicine School of Nanjing University, Nanjing, Jiangsu Province, China.
出版信息
J Surg Res. 2011 Jul;169(1):e85-91. doi: 10.1016/j.jss.2011.03.060. Epub 2011 Apr 20.
BACKGROUND
Vascular smooth muscle cell (VSMC) proliferation plays an important role in the failure of autologous vein grafts. The c-myc gene activation is highly involved in the VSMC proliferation. In this study, we made an attempt to determine whether VSMC proliferation and vein graft restenosis could be attenuated by silencing the c-myc gene with small interference RNA (siRNA).
METHODS
The effects of c-myc siRNA on VSMCs in vitro were examined both in cell proliferation and c-myc expression. Thirty-two Sprague-Dawley rats underwent autologous jugular vein to carotid artery reverse interposition grafting and were randomly divided in to four groups. Vein grafts were treated with pluronic gel or gel containing a scrambled siRNA or c-myc siRNA and the control group received no treatment. Intimal thickness of the vein grafts was evaluated at 3 wk after the surgery.
RESULTS
In vitro, c-myc siRNA inhibited cell proliferation by 40%, reduced c-myc mRNA level by 70%, and c-myc protein level by 50% compared with the controls. In vivo, the c-myc siRNA treatment reduced intimal hyperplasia by 75%.
CONCLUSIONS
Our data suggested that c-myc siRNA, when given immediately after the surgery, is an effective approach for the prevention of vein graft restenosis.
背景
血管平滑肌细胞（VSMC）增殖在自体静脉移植物失败中起着重要作用。c-myc 基因的激活高度参与了 VSMC 的增殖。在这项研究中，我们试图通过用小干扰 RNA（siRNA）沉默 c-myc 基因来确定 VSMC 增殖和静脉移植物再狭窄是否可以得到缓解。
方法
在体外通过细胞增殖和 c-myc 表达来检测 c-myc siRNA 对 VSMCs 的影响。32 只斯普拉格-道利大鼠进行了自体颈静脉到颈总动脉逆行转位移植，并随机分为四组。静脉移植物用 pluronic 凝胶或含有乱序 siRNA 或 c-myc siRNA 的凝胶处理，对照组不接受任何治疗。术后 3 周评估静脉移植物的内膜厚度。
结果
在体外，c-myc siRNA 抑制细胞增殖 40%，降低 c-myc mRNA 水平 70%，c-myc 蛋白水平 50%，与对照组相比。在体内，c-myc siRNA 处理使内膜增生减少 75%。
结论
我们的数据表明，c-myc siRNA 在手术后立即给予时是预防静脉移植物再狭窄的有效方法。
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