重组腺病毒携带TNF-α受体Ⅰ基因对肝脏缺血再灌注损伤的研究  

Experimental study on protective effect of sTNFR genes in the hepatic ischemia reperfusion of rat

作　　者：张培影[1,2] 郝林[3] 张勇[4] 鲍红光[4] 贡震[3] 郑巍[5] 詹鸣[5] 韩从辉[3] 

机构地区：[1]南京中医药大学第一临床医学院,210029 [2]东南大学肿瘤研究所 [3]东南大学医学院附属徐州医院泌尿外科 [4]南京医科大学附属南京第一医院麻醉科 [5]中山大学第五医院泌尿外科

出　　处：《中华临床医师杂志（电子版）》2009年第11期53-56,共4页Chinese Journal of Clinicians(Electronic Edition)

基　　金：江苏省自然科学基金(BK2009085);广东省珠海市科委基金(20041051)

摘　　要：目的探讨大鼠肝脏缺血再灌注损伤的过程和相关机制及可溶性TNF-α受体Ⅰ(sTNFRⅠ)基因的保护作用。方法预先给予携带sTNFRⅠ基因的重组腺病毒后建立大鼠缺血再灌注模型,阻断肝左、中叶入肝血流60min后分别再灌注1h、3h、6h、12h。采用全自动生化分析仪测定血清中肝酶学指标(AST、ALT),TBA法测定肝脏丙二醛(MDA)含量。大鼠肝脏组织切片HE染色后,行光镜检查,观察肝组织显微结构变化。结果AST、ALT和肝脏的组织形态学都显示模型组较假手术组大鼠有明显的肝脏损伤,其中以再灌注6h肝脏损伤最严重。肝组织MDA含量明显高于假手术组(P<0.01),于再灌注3h达到高峰。肝组织TNF-α的表达均明显高于假手术组(P<0.01),且于再灌注6h达到高峰。结论sTNFRⅠ可增强抗氧化能力,降低MDA水平,抑制缺血再灌注大鼠体内氧化应激水平,对大鼠缺血再灌注有一定的治疗作用。Objective To investigate the process and mechanisms in the hepatic ischemia/ reperfusion injury, of rat, and the protective effect of sTNFR genes. Methods Constitute the model of ischemia/reperfusion injury in the rat, then the rats were subjected to 60 min of sustained occlusion of the blood for left and middle liver followed by 1 hours,3 hours,6 hours and 12 hours of reperfusion. Detect the activity of alanine AUF and AST in the blood ; the activity of malondialdehyde（MDA） in the liver tissues were assessed. The microscopical structure of the liver tissue were observed by HE staining. Results The activities of ALT, AST were all obviously damaged at the end of reperfusion respectively in the I/R group of rat. At the point of reperfusiou 6 h, hepatic injury was the most serious ;The activity of MDA in I/R group was higher than Sham group （P 〈 0. 01 ）, and reach the lowest point at after reperfusion 6 h. The expression of TNF-α was lower than the same time of I/R group （ P 〈 0. 05 ）. Conclusions These data indicate that adenovirus-mediated sTNFR gene has protective effect against hepatic ischemia/reperfusion injury by enhancing the ability of eliminating oxygen free radicals ;inhibiting the activation and expression of inflammation.

关 键 词：肝切除术 肝移植 受体 肿瘤坏死因子 缺血 再灌注损伤 模型 动物 

分 类 号：R575[医药卫生—消化系统]