摘要
目的采用基因芯片技术检测乌司他丁（UTI）预处理脓毒症大鼠的脑组织基因表达，并分析推论其可能的作用机制。方法45只雄性Wistar大鼠按随机数字表法等分为对照组、脓毒症组和UTI组。采用盲肠结扎穿孔术（CLP）复制脓毒症大鼠模型；对照组仅开腹、关腹，不行CLP。UTI组于制模前1h肌肉注射（肌注）UTI 100kU／kg；脓毒症组及对照组肌注平衡液5ml／kg。采用RatRef-12大鼠表达谱基因芯片进行检测，用计算机软件筛选并分析比较脓毒症组和UTI组与对照组大鼠脑组织基因表达的变化，并初步分析脓毒症组和UTI组表达基因之间的差异。结果在22523个基因中，与对照组比较，脓毒症组大鼠脑组织差异表达基因共55个，占基因芯片总点数的0．244％；其中表达下调者47个，已知功能基因23个；表达上调者8个，已知功能基因6个。与对照组比较，UTI组大鼠脑组织差异表达基因共82个，占基因芯片总点数的0．364％；其中表达下调者66个，已知功能基因39个；表达上调者16个，已知功能基因8个。与对照组比较，脓毒症组与UTI组有同向表达的基因19个，其中下调18个，包括Adora2a、Avp、Cart、Gng7、Myh7、Oxt、Pde1b、Pdyn、Prkcd、Prkch、Rgs9、Rxrg、Six3、Slc17a6、Slco1a5、Sostdc1、Tac1、Ttr；上调1个，为S100a8。结论脓毒症时存在脑功能障碍相关的基因表达紊乱；UTI预处理可部分纠正脓毒症大鼠过度炎症反应及免疫抑制所致脑组织基因表达异常，从基因水平上对脑组织起到保护作用；同时脓毒症时机体可能存在一定的自我调节作用，一定程度上对脑组织具有保护作用。
Objective To detect the differences in gene expression of brain tissue in septic rats with ulinastatin（UTI）preconditioning with DNA microarray. Methods Forty-five male Wistar rats were equally divided into control group, sepsis group, and UTI group by means of random number table. In UTI group the rats were treated with intramuscular injection of UTI （100 kU/kg） 1 hour before cecal ligation and puncture （CLP）. In sepsis group and control group intramuscular balanced solution （5 ml/kg） instead of UTI was given. Septic rat model was reproduced by CLP. The control group underwent a simulated operation without CLP. Gene expression profile was studied by using RatRef-12 rat gene expression profile microarray to detect the changes in gene expression pattern of rat brain tissue after CLP. Then related computer software was used to screen and analyze the relationship between the sepsis/UTI group and control group. Finally, the difference between the sepsis group and UTI group was analyzed. Results In 22 523 genes, 55 differential genes were found between sepsis group and control group, accounting for 0. 244%. Among them 47 genes showed down-regulation, with 23 known functional genes; 8 genes showed up-regulation, with 6 known functional genes. Eighty-two differential genes were found between UTI group and control group, accounting for 0. 364%. Among them 66 genes showed down-regulation, with 39 known functional genes; 16 genes showed up-regulation, with 8 known functional genes. When sepsis group and UTI group compared with control group, 19 genes showed the same degree of regulation,with 18 genes （Adora2a, Avp, Cart, Gng7, Myh7, Oxt, Pdelb, Pdyn, Prkcd, Prkch, Rgs9, Rxrg, Six3, Slc17a6, Sleola5, Sostdcl, Tacl, Ttr） showed down-regulation and 1 gene （S100a8） showed up-regulation. Conclusion UTI preconditioning can partly adjust abnormal expression of genes in the brain tissue of rat with sepsis in the presence of excessive inflammation and immune suppression. UTI has some degree of protective effect on brain at the genetic level. Meanwhile, there is certain self regulation in the body during sepsis.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2011年第8期490-494,共5页
Chinese Critical Care Medicine
基金
天普研究基金项目（01200912）
