目的 研究自體靜脈移植后早期生長反應基因-1（Egr-1）表達的動態(tài)變化，探討其在內(nèi)膜增生中的作用。方法 Wistar大鼠90只，將大鼠右頸總靜脈端-端吻合于腎下腹主動脈建立自體靜脈移植模型。術(shù)后隨機分別于1、2、6 和24 h，3、7、14、28及42 d相應時間處死動物取移植靜脈，同時取正常靜脈作對照。應用原位雜交和RT-PCR方法檢測Egr-1 mRNA的表達，聯(lián)合應用Western蛋白印跡和免疫組織化學方法檢測Egr-1蛋白表達情況，同時進行組織形態(tài)學觀察。結(jié)果 自體靜脈移植后，Egr-1 mRNA和Egr-1蛋白的表達呈雙相變化，即移植后1 h, Egr-1 mRNA表達迅速升高，陽性率為（35±7）%，6 h、24 h及3 d時下降到較低水平，陽性率分別為（8±2）%、（8±6）%和（8±4）％，7 d時又再升高，28 d時達高峰，陽性率為（45±6）%，此與其余各時點比較差異均有統(tǒng)計學意義（P＜0.01），42 d時，Egr-1 mRNA的表達再次下降； 移植早期（2 h）即有Egr-1蛋白的表達，陽性率為（30±5）%，并持續(xù)至6 h，24 h～3 d表達下降到較低水平，陽性率分別為（7±3）%和（7±8）%，7 d時又再升高，至移植后28 d，Egr-1蛋白的表達陽性率達到高峰，為（40±9）%，此與其余各時點比較差異有統(tǒng)計學意義（P＜0.01）。移植后7 d，免疫組化結(jié)果顯示，Egr-1蛋白表達主要位于中膜血管平滑肌細胞（VSMCs）和單核細胞/巨噬細胞，移植后期28 d，Egr-1蛋白表達主要位于新生內(nèi)膜和中膜的VSMCs，同時部分內(nèi)皮細胞也有Egr-1蛋白的表達。結(jié)論 移植靜脈內(nèi)膜增生與Egr-1的激活及表達關(guān)系密切，Egr-1可能成為防治移植靜脈內(nèi)膜增生、狹窄及閉塞的一個新的干預靶點。
引用本文： 劉程偉,胡新華,張雪松,楊軍,羅英偉,王新文,張強. Egr-1在自體移植靜脈中的表達及意義. 中國普外基礎與臨床雜志, 2006, 13(6): 642-646. doi: 復制
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- 2. Harja E, Bucciarelli LG, Lu Y, et al. Early growth response-1 promotes atherogenesis: mice deficient in early growth response-1 and apolipoprotein E display decreased atherosclerosis and vascular inflammation [Ｊ]. Circ Res， 2004; 94(3)∶333.
- 3. Sukhatme VP, Cao XM, Chang LC, et al. A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular dep [Ｊ]. Cell， 1988; 53(1)∶37.
- 4. Yan SF, Fujita T, Lu J, et al. Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress [Ｊ]. Nat Med, 2000; 6(12)∶1355.
- 5. Blaschke F, Bruemmer D, Law RE, et al. Egr-1 is a major vascular pathogenic transcription factor in atherosclerosis and restenosis [Ｊ]. Rev Endocr Metab Disord， 2004; 5(3)∶249.
- 6. Wada Y, Suzuki J, Kawauchi M, et al. Early growth-response factor 1 and basic transcriptional element-binding protein 2 expression in cardiac allografts [Ｊ]. J Heart Lung Transplant， 2001; 20(5)∶590.
- 7. Ohtani K, Egashira K, Usui M, et al. Inhibition of neointimal hyperplasia after balloon injury by cis-element ‘decoy’ of early growth response gene-1 in hypercholesterolemic rabbits [Ｊ]. Gene Ther， 2004; 11(2)∶126.
- 8. Fahmy RG, Khachigian LM. Locked nucleic acid modified DNA enzymes targeting early growth response-1 inhibit human vascular smooth muscle cell growth [Ｊ]. Nucleic Acids Res， 2004; 32(7)∶2281.