The Effect Of Ulinastatin On Gene Expression Of Myocardial Energy Metabolism In Septic Rats

Sepsis is systemic inflammatory response syndrome(SIRS) caused by infection.Myocardial dysfunction frequently occurs in severe sepsis and septic shock. However,its mechanisms remain unclear. Myocardial energy metabolism disorder is one of the initial events of the damage of cardiac muscle cells, which is the important factor affect the incidence and development of Myocardial dysfunction. The diagnosis and treatment of sepsis and sepsis shock is always improving, in addition to the classic anti-infection treatment, fluid resuscitation, protective ventilation, etc., some adjuvant therapy have been focused to clinical use, including the use of corticosteroids, the use of immunoglobulin, the application of anticoagulant, control of blood sugar, the application of statins, the use of ulinastatin and so on. Ulinastatin(UTI) is the protease inhibitor extracted from the urine, which can inhibit protease(such as trypsin, elastase,fibrinolytic enzymes) and sugar and lipid hydrolytic enzymes(Such as hyaluronidase,amylase, lipase). At present there are few researches about the effect of ulinastatin on sepsis myocardial energy metabolism, especially on the genetic level. This experiment was designed to explore the effect of ulinastatin(UTI) on sepsis myocardial energy metabolism and infer the possible mechanism at the level of genes.Methods: 45 male Wistar rats were randomly divided into control group, sepsis group and ulinastatin group. Cecal ligation and puncture(CLP) was used to produce rat sepsis model; The control group only experience experienced a simulated operation without CLP. In UTI group the rats were treated with intramuscular injection of UTI100 kU/kg 1 hour before CLP.Every 8 hours repeated the doses in UTI group, In sepsis group and control group balanced electrolyte solution(5ml/kg)was given. In 24 h after CLP, the rats were killed after anaesthetized by ketamine, then took the heartsample and immediately put into liquid nitrogen,- 70 ?, for extracting RNA. RT2 profile PCR array was used to analysis and compare the differently expressed myocardial energy metabolism genes of sepsis and ulinastatin group, and to find out the different of the differently expressed genes between the sepsis and ulinastatin group.Results: the gene expression changes of myocardial energy metabolism were both found in sepsis group and ulinastatin group. 11 differential genes were found in ulinastatin group compared with control group, and among them 9 genes(Atp12a Atp4 a Atp5d, Atp6v0a2, Atp6v1g3, Cox4i2, Cyc1, Slc25a10, Slc25a15) showed down-regulation, 2 genes(Atp6v0d2, Atp6v1e2) showed up-regulation; In Sepsis group,5 differential genes were found, among them 2 genes(Atp6v1g3, Ucp1) showed down-regulation, 3 genes(Atp12a Atp4 a Ucp3) showed up-regulation. The differential genes of Ulinastatin group and sepsis group is different. 13 regulation genes of ulinastatin were found. The proteins encoded by the regulation genes include respiratory chain enzyme complexes V(ATP synthase), enzyme complex IV(cytochrome c oxidase), enzyme complex III(coenzyme Q- cytochrome c reductase), and accessory protein(about energy metabolism).Conclusion: Sepsis make myocardial energy metabolism change. Ulinastatin improve the myocardial energy metabolic disorders induced by sepsis to a certain extent.