[The effect of ulinastatin on gene expression of brain tissue in septic rat].

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, Pde1b, Pdyn, Prkcd, Prkch, Rgs9, Rxrg, Six3, Slc17a6, Slco1a5, Sostdc1, Tac1, 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.

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

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.