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Background endotoxemia systemic inflammation caused by trauma, infection or (and) hair syndrome (systemic inflammatory response syndrome, SIRS), the heart is one of the commonly affected organs of septic shock, in the event of cardiac dysfunction, mortality immediately increased from 20% to 70-90%, the tenth largest cause of inpatient death. Recent studies have found to improve heart function can significantly improve the survival rate of sepsis patients. Therefore, committed to improving cardiac function in patients with sepsis, has become a hot direction of the therapeutic value of clinical and basic research. TLR4/NF-κB excessive activation of signaling pathways and the resulting excessive inflammatory response, important factors of heart failure caused by endotoxemia. Imbalance between systolic and diastolic function of the vascular endothelium, increased vascular permeability caused by inflammatory cells and inflammatory mediators, but also infectious the shock cardiac dysfunction during the development of the key molecular events within the myocardial infiltration. Many in vitro and in vivo studies have found that PI3K/Akt signaling pathway is a negative regulator of the inflammatory response. Heat shock protein A12B (Heat shock protein A12B, HSPA12B) the Han Zhihua equal to 2003 for the first time in human atherosclerotic plaques in the cloned gene. Further study found HSPA12B mainly expressed in vascular endothelial cells, is the newest member of the family of heat shock protein 70, vascular endothelial cell proliferation, migration, angiogenesis indispensable,, and found HSPA12B promote angiogenesis and activation of Akt signaling pathway. However, in the relevant disease occurrence and development HSPA12B yet to see any reports. Objective To study the expression of high impact and mechanisms of HSPA12B ventricular dysfunction caused by endotoxemia in mice. Method 1. Experimental animals: high expression human HSPA12B gene in transgenic mice (Hspa12b transgenic mice, HSPA12B Tg) work together to build our group, mode of Nanjing University, Institute of Zoology, University of East Tennessee Professor Han Zhihua Laboratory, housed in the mode of Nanjing University animal studies the SPF animal room. Endotoxemia model established :8-10-week-old female HSPA12B Tg littermates born to wild-type female mice (wide type, WT) by intraperitoneal injection (Intraperitoneal Injection IP) bacterial endotoxin (lipopolysaccharide, LPS)-induced endotoxemia model, injecting a dose of 10mg/kg. 3 Determination of cardiac function: LPS six hours after intraperitoneal injection, mice with mouse heart-dimensional ultrasound evaluation of left ventricular systolic function parameters. Inhibit the PI3K/Akt pathway: after wortmannin (1mg/kg) intraperitoneal injection of 1 hour, and then by intraperitoneal injection of LPS (10mg/kg). Western Blot: for the analysis of I-κBα (Inhibitor of nuclear factor-kappa B), intercellular adhesion molecule -1 (ICAM-1) and vascular cell adhesion molecule -1 (VCAM-1), Angiopoietin-1 (Ang -1), endothelial nitric oxide synthase (endothelial NO synthase, eNOS), inducible nitric oxide synthase (inducible nitric-oxide synthase, iNOS) expression levels, as well as Akt and its downstream target molecule of glycogen synthase -3β (Glycogen Synthase Kinase3β, GSK-3β) phosphorylation levels. 6 Accountancy processing: data expressed as mean ± standard deviation (x ± s) were statistically analyzed using Stata 7.0 software was used for statistical ANOVA analysis of variance, the two groups were compared using the Scheffe method P lt; 0.05 means that differences statistically significant. Results, the 1 HSPA12B expression significantly reduced LPS-induced heart failure, left ventricular ejection fraction (Ejection Fraction, EF) and fractional shortening (Fraction shortening, FS) compared with the LPS-treated WT mice, respectively. LPS administration, WT mice cardiac tissue I-κBα degradation, the degradation significantly reduce expression of HSPA12B high. 3 after LPS administration, ICAM-1 and VCAM-1 was significantly increased, but the extent of its elevated expression of HSPA12B high significantly reduced. 4 LPS administration, vascular permeability in the myocardial tissue significantly increased, but significantly reduced LPS-induced vascular hyperpermeability expression of HSPA12B high. LPS administration, the myocardial tissue level of phosphorylation of Akt and GSK-3β decreased, but the decrease in Tg mice than WT mice reduced significantly. The selective inhibition of the PI3K/Akt signaling pathway, to the protective effect induced by endotoxin in addition to the high expression of HSPA12B ventricular dysfunction.
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