摘要
目的观察硼替佐米对大鼠移植静脉内膜增生的抑制作用。方法取Wistar大鼠76只，进行自体静脉移植并随机分为硼替佐米组和安慰剂组，分别在术后第0、3、7、10天静脉注射0．15mg／kg硼替佐米或等体积生理盐水。在术后24、72h处死大鼠，取移植静脉行逆转录．聚合酶链反应（RT—PCR）及酶联免疫吸附试验（ELISA）检测中性粒细胞趋化因子（CINC）-213、单核细胞趋化蛋白（MCP）-1、白细胞介素（IL）-1、IL-6及肿瘤坏死因子（TNF）-a水平，并进行中性粒细胞趋化实验；在术后4周处死大鼠，取移植静脉行组织病理学检查。结果术后4周移植静脉内膜增生明显（70．93±11．25）um（P〈0．05），炎症相关因子蛋白水平在术后24h均显著增高CINC．213（415．23±56．50）pg/mg、MCP-1（9894．58±2795．62）pg／mg、IL-1（3087．51±609．19）pg／mg、IL-6（2225．27±206．06）pg／mg、TNF—a（402．31±134．13）pg／mg（P〈0．05）；应用硼替佐米可明显抑制除IL-1外各检测因子的表达合成CINC-2β（231．48±36．32）pg／mg、MCP—1（5846．10±1044．33）pg／mg、IL-6（1023．22±109．84）pg／mg、TNF—a（218．40±38．06）pg/mg（P〈0．05）及移植血管对中性粒细胞的趋化指数（241．52±33．43）％vs（167．81±30．00）％（P〈0．05），并明显抑制移植静脉的内膜增生（35．23±5．21）um（P〈0．05）。结论硼替佐米可明显抑制移植静脉术后的炎性变化和内膜增生。
Objective The anti-inflammatory and vaso-proteetive effects of bortezomib were analyzed in rat model to test whether it inhibits neointima formation in transplant-induced vasculopathy. Methods Seventy-six rats were subjected to autologous vein grafting surgery. Thereafter, all post-surgical rats were randomly divided into two groups and dosed intravenously with 0. 15 mg/kg bortezomib or vehicle on the day 0, 3, 7, and 10. After 24 and 72 h, rats were humanely killed and vein grafts were processed for real-time reverse transeription-polymerase chain reaction （RT-PCR） to test the gene expression of cytokineinduced neutrophil ehemoattractant-2（3 （ CINC-2β ）, monocyte ehemoattractant protein （MCP） -1, intedeu- kin （IL）-1, IL-6 and tumor necrosis factor （TNF）-a. Meanwhile, 24-h vein grafts were processed for enzyme linked immunosorbent assay （ELISA） or neutrophil chemotaxis assay. Subsequently, rats were euthanized at 4th week after grafting and samples were processed for morphometric analysis. Results The expression of mRNA for ehemokines （ CINC-2β, MCP-1 ） and eytokines （ IL-1, IL-6 and TNF-a ） were markedly increased in the injured vessels at the first day after surgery and declined during the following three days, and protein levels of them were markedly increased at the same time [ CINC-2β （415.23 ± 56. 50） pg/mg; MCP-1 （9894. 58 ±2795.62） pg/mg; IL-1 （3087. 51 ±609. 19） pg/mg; IL-6 （2225.27 ± 206. 06） pg/mg; TNF-a （402. 31 ± 134. 13 ） pg/mg ] （P 〈 0. 05 ） accompanied with a marked increase in neutrophil migration toward homogenates of injured vessels as chemotactic index （CI） was （241.52 ± 33.43） % （ P 〈 0.05 ）. Morphometric analysis revealed that the intima of grafts was thickened markedly as （70. 93 ± 11.25 ） um at 4th week after surgery （ P 〈 0. 05 ）. It was important that bortezomib significantly attenuated gene expression and protein levels in most of the inflammatory mediators except IL-1 [ CINC-2β （231.48 ±36.32） pg/mg; MCP-1 （5846. 10 ±1044.33） pg/mg; IL-6 （1023.22 ±109.84） pg/mg; TNF-a （218.40 ± 38. 06） pg/mg] （P 〈 0. 05 ）, and simultaneously inhibited neutrophil chemotactic activity of the vessel homogenates as CI was （167.81 ±30. 00）% （P 〈0. 05）. And notably, bortezomib resuited in significant inhibition of intimal hyperplasia as （35.23 ± 5.21 ） um at 4th week compared with untreated controls （P 〈 0. 05）. Conclusion Bortezomib could inhibit neointima formation by attenuating the inflammatory response in transplant-induced vasculopathy.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2011年第12期2114-2117,共4页
Chinese Journal of Experimental Surgery
