乌司他丁对脓毒症大鼠心脏组织基因表达的影响

Objective To observe the regulatory effect of ulinastatin (UTI)preconditioning on gene expression of heart tissue in septic rats by DNA microarrays.Methods Forty-five male Wistar rats were equally divided into control group, sepsis group and UTI 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 1 hour before CLP.In sepsis group and control group balanced electrolyte solution (5 ml/kg) was given.Gene expression spectrum was studied with RatRef-12 rat gene expression profile microarray to detect the changes in gene expression pattern of rat heart tissue after CLP.Genes with fluorescent signal of Cy3/Cy5 of ratio average (RA)＞2.0 or RA＜0.5 were identified as differential genes,and those highly correlated to sepsis and UTI groups were screened by means of related computer software to analyze their relationship.Results In 22 523 genes,418 differential genes were found in sepsis group compared with control group,accounting for 1.856%, and among them 200 genes showed up-regulation, with 84 known functional genes,and 43 of which only showed up-regulation in sepsis group,but normal in UTI group.Two hundred and eighteen genes showed down-regulation, with 74 known functional genes, 37 of which only showed down-regulation in sepsis group, but normal in UTI group.Two hundred and two differential genes were found in UTI group compared with control group, accounting for 0.897%, and among them 111 genes showed up-regulation, with 57 known functional genes, and 17 of which only showed up-regulation in UTI group, but normal in sepsis group.Ninety-one genes showed down-regulation, with 48 known functional genes, 18 of which only showed down-regulation in UTI group, but normal in sepsis group.Compared with the control group, in both UTI group and sepsis group, 41 of known functional genes showed up-regulation,and 37 showed down-regulation.Conclusion UTI preconditioning can ameliorate the damage to heart tissue in rat sepsis model, thus it has a protective effect on heart, and its mechanism may be attributable to regulatory effect of UTI on expression of stress reaction, cell signal transduction, energy metabolism,immune reaction and other related genes.

Effect of ulinastatin preconditioning on gene expression profile of heart tissue in a rat sepsis model