CAJ | 학술논문

目的应用基因芯片技术研究乌司他丁(UTI)预处理对脓毒症大鼠肾组织基因表达的调控.方法按随机数字表法将45只Wistar大鼠分为对照组、脓毒症组、UTI组,每组15只.采用盲肠结扎穿孔术(CLP)复制脓毒症大鼠模型;对照组行开腹、关腹,但不予CLP.UTI组于制模前1 h肌肉注射UTI 100 kU/kg,脓毒症组及对照组给予平衡液5 ml/kg.采用含有22 523个大鼠基因cDNA克隆的表达谱基因芯片进行检测,以Cy3和Cy5两种荧光信号强度结果比值均>2.0或<0.5的基因为表达差异基因,用计算机软件筛选并分析脓毒症组/对照组、UTI组/脓毒症组大鼠肾组织的基因表达变化,并初步分析差异表达基因与脓毒症及UTI预处理之间的关系.结果脓毒症组/对照组共筛选出327个表达差异基因,占基因芯片总点数的1.45%;其中表达上调者181个,已知功能基因78个;表达下调者146个,已知功能基因51个.UTI组/脓毒症组共筛选出127个表达差异基因,占基因芯片总点数的0.56%;其中表达上调者41个,已知功能基因14个;表达下调者86 个,已知功能基因37个.脓毒症组/对照组下调的同时在UTI组/脓毒症组中上调的基因22个,其中已知功能基因11个;脓毒症组/对照组上调的同时在UTI组/脓毒症组中下调的基因51个,其中已知功能基因24个.结论 UTI预处理可减轻脓毒症大鼠肾组织的损害,具有一定的肾脏保护效应,其机制涉及UTI对免疫反应、细胞物质能量代谢、炎症反应、信号转导、防御应答、氧化还原反应、DNA复制、转录调节等方面相关基因表达的调控.
목적 응용기인심편기술연구오사타정(UTI)예처리대농독증대서신조직기인표체적조공.방법 안수궤수자표법장45지Wistar대서분위대조조、농독증조、UTI조,매조15지.채용맹장결찰천공술(CLP)복제농독증대서모형;대조조행개복、관복,단불여CLP.UTI조우제모전1 h기육주사UTI 100 kU/kg,농독증조급대조조급여평형액5 ml/kg.채용함유22 523개대서기인cDNA극륭적표체보기인심편진행검측,이Cy3화Cy5량충형광신호강도결과 비치균>2.0혹<0.5적기인위표체차이기인,용계산궤연건사선병분석농독증조/대조조、UTI조/농독증조대서신조직적기인표체변화,병초보분석차이표체기인여농독증급UTI예처리지간적관계.결과 농독증조/대조조공사선출327개표체차이기인,점기인심편총점수적1.45%;기중표체상조자181개,이지공능기인78개;표체하조자146개,이지공능기인51개.UTI조/농독증조공사선출127개표체차이기인,점기인심편총점수적0.56%;기중표체상조자41개,이지공능기인14개;표체하조자86 개,이지공능기인37개.농독증조/대조조하조적동시재UTI조/농독증조중상조적기인22개,기중이지공능기인11개;농독증조/대조조상조적동시재UTI조/농독증조중하조적기인51개,기중이지공능기인24개.결론 UTI예처리가감경농독증대서신조직적손해,구유일정적신장보호효응,기궤제섭급UTI대면역반응、세포물질능량대사、염증반응、신호전도、방어응답、양화환원반응、DNA복제、전록조절등방면상관기인표체적조공.
Objective To investigate the modulation effect of ulinastatin (UTI) preconditioning on gene expression of kidney tissue in septic rats by DNA microarrays. Methods Forty-five male Wistar rats were divided into control group, sepsis group and UTI group, with 15 rats in each group by means of random number table. Cecal ligation and puncture (CLP) was used to reproduce rat sepsis model. The control group only experienced a simulated operation without CLP. In UTI group the rats were treated with intramuscular injection of UTI (100 kU/kg). In sepsis group and control group intramuscular balanced solution (5 ml/kg) was given. Gene expression spectrum was studied with oligonucleotide gene expression profile microarray that contained 22 523 rat cDNA clones to detect the changes in gene expression pattern of rat kidney tissue 24 hours after CLP. Genes with fluorescent signal of Cy3/Cy5 of ratio average (RA)>2.0 or RA<0.5 were identified as differential genes, then those highly correlated to sepsis and UTI were screened by means of related computer software, and their relationship was analyzed. Results Three hundred and twenty-seven differential genes were found in sepsis group/control group, accounting for 1.45%, and among them 181 genes showed up-regulation,with 78 known functional genes, and 146 genes showed down-regulation, with 51 known functional genes. One hundred and twenty-seven differential genes were found in UTI group/sepsis group, accounting for 0.56%, and among them 41 genes showed up-regulation, with 14 known functional genes, and 86 genes showed down-regulation, with 37 known functional genes. Twenty-two genes were down-regulated in sepsis group/control group but up-regulated in UTI group/sepsis group, with 11 known functional genes, 51 genes were up-regulated in sepsis group/control group but down-regulated in UTI group/sepsis group, with 24 known functional genes. Conclusion UTI preconditioning can alleviate the damage of kidney tissue in rat sepsis model, thus showing a protective effect on kidney, and the mechanism may be attributable to effect of UTI on modulation of immune reaction, energy metabolism, inflammatory reaction, signal transduction, defense reaction, oxydation-reduction reaction, DNA replication, and transcription related genes.