| Objective: Through the observation of expression level ofjanus kinase/signal transduction and transcriptional activation factor(JAK/STAT) mRNA gene、the STAT3protein and proinflammatorycytokines TNF alpha、 IL-6expression level in the lung tissue of sepsismice model, the severity inflammatory response of sepsis mice model,which was producted into sepsis mice model by injecting endotoxininto enterocoelia and was given exogenous ghrelin as intervention, Todiscuss the regulating role of Ghrelin in the inflammatory response ofsepsis, to furtherly clarify the pathogenesis of sepsis and to explore theinflammation reaction mechanism what ghrelin regulated in sepsis, and tolook for new way of improving the cure rate of sepsisMethods：1, injecting endotoxin into enterocoelia of mice as theclassic way of sepsis model was set up, while inject (ghrelin200ug/kg)into enterocoelia of mice as intervention treatment, intraperitonealinjection equivalent amount of saline as a control was injected intoenterocoelia of mice. Selectling54female kunming mice, weighted20to25g, three groups which were controlled group, model group andintervention group with ghrelin were randomly divided, each groupcontains18mice, only A (controling group): saline was injected into abdominal cavity of mice.Model group (B) with treated:lipopolysaccharide6mg/kg was injected into abdominal cavity; C(intervention group): first injecting the ghrelin200ug/kg into abdominalcavity, after30minutes injecting lipopolysaccharide6mg/kg into theabdominal cavity of mice;2、each group respectively in3hours,9hoursand18hours executed6mice randomly, collect specimen tocorresponding test.1） take each experimental group organization of theright upper lobe, for HE staining, then observe the lung tissue pathology.A.2）using enzyme linked immunosorbent (ELISA) to determinateinflammation factor TNF alpha, IL-6, stat3expression level of left upperlobe.3）RT-PCR method was used for detecting expression of stat3mRNA with the double under lung lobe.3, the software of SPSS17wasapplicated to statistical analysis of data, data was expressed with (mean+standard deviation). Comparison between groups using single factoranalysis of variance, using Pearson correlation to analysis the correlationof stat3、TNF alph and IL-6.Results:1, in HE dyed,the controlgroup of the lung tissue structure complete, airway epithelial cells neat,without interstitial edema and obvious inflammatory cells immersed, nobleeding, alveolar cavity is complete, without edema fluid;at Each timepoint the model group is a large number of inflammatory cells infiltrationand diffusion in the pulmonary interstitial and alveolar damage structure,part of epithelial cells deformation, pulmonary interstitial edemaing, alveolar septum thickening, alveolar cavities appear edema exudate,blood capillary dilating, alveolar space was cavity filled with red bloodcells, with alveolar hemorrhage and alveolar wall structures destruction,3hours after building visible sepsis,inflammation effusion typicalpathological changes, most serious inflammation was at9hours afterthe building,18hours alveolar cavities are visible cellulose seepage,hyperplasia of the change; pathological lung tissue inflammation changesof intervention group with Ghrelin obviously alleviated at the same timepoints compared with the model group.2, model group and interventiongroup in lung tissue homogenate stat3mRNA expression were increasedsignificantly With control groupCompare，with statistically significantdifference (P <0.001)， The expression of lung tissue in interventiongroup at various time points were decreased Compared with the modelgroup, with statistically significant (P values <0.001).3, model groupand intervention group lung tissue homogenate stat3mRNA increases, intime consistency accompanying the rise of early inflammatory cytokinesTNF-a、 IL-6in the lung tissue homogenate, increase was mostpronounced in nine hours, with statistically significant differencecompared with control group (P <0.001). while compared with modelgroup, the intervention group with the expression of inflammatory factorsdeclined in each time point, the difference was statistically significant (P<0.001).4, model group and intervention group of STAT3protein expression in lung tissue homogenate was elevated compared withcontrol group at each time point, with statistically significant (P values <0.001), and in line with stat3mRNA changes in lung tissue homogenate,correlation analysis of STAT3.TNF-a and IL-6are positively relatedcorrelation, the correlation coefficient were0.88,0.91. Protein expressionof stat3in the intervention group and TNF alpha、 IL-6in theexpression in lung tissue also has relevance,they are positively related,with the correlation coefficient of0.88,0.88,Conclusions: Gavenexogenous ghrelin into spesis mice as intervention can improve theinflammatory cells infiltration of sepsis mice lung tissue, reduce theactivation of transcription factors STAT3mRNA and STAT3proteinexpression levels, at the same time accompanied by dropinginflammatory cytokines (TNF-a and IL-6) expression, ghrelin involvedin the regulation of the inflammatory cascade amplification reaction ofsepsis, its regulating inflammatory response mechanism may be related toinhibiting janus kinase/signal transduction and transcriptional activationfactor (jak/stat) pathway. |
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