Role Of Tissue Factor Expression Mediated By NF-κB Under Inflammatory Stress In Coagulation Disorders

Part I Clinical and Pathological Correlation Between Inflammation and Pulmonary ThromboembolismObjective:To provide a reference for preventing this disease by means of analyzing the critical risk factors resulting in pulmonary thromboembolism. Methods:The data of patients who died of pulmonary thromboembolism were analyzed retrospectively. The clinical data was collected on age, gender, medical history, treatment etc. Autopsy data collected on introduction of the case, the autopsy observation, microscope observation, pathologic diagnosis, laboratory examination and the cause of death analysis. Results:There were 51 patients (male 27 and female 24 aged 13～81, average aged 47.12±15.82); they were acute onset and died in a short time; The thrombus mainly originated in deep vein of lower limbs; 49 cases had obvious infection,43 of them had respiratory infection; 36 of them had trauma or operation; only 2 had trauma but no infection. Conclusions:The PTE cases were complicated with infection, trauma or other inflammatory status; especially the respiratory system infection had close relationship with pulmonary embolism.Part Ⅱ Tissue Factor Expression induced by NF-κB under Inflammatory Stress in RatsObjective:To explore the expression of NF-κB and TF in monocytes of rats and the mechanism of coagulation disorders under inflammatory stress. Methods:32 SD rats were randomly assigned to 4 groups. The control group, Casein group, Streptococcus pneumonia group (SP group), Pseudomonas aeruginosa group (PA group),8 rats in each group. The Casein group was induced by injecting 6ml 12% casein into abdominal cavity. The SP group was induced by intranasal drip of SP (9×108 CFU/ml) with 0.12ml.The PA group was induced by intranasal drip of PA (9×108 CFU/ml) with 0.12ml.48 hours later, we observed the morphological changes of lung tissue and tested the level of blood routine, hs-CRP, D-dimer and the thrombosis in heart and blood vessels. We tested the mRNA expression of NF-κB p65, TF by Real-Time PCR and the protein expression of p-p65,p-IκBa and TF by Western Bolt and then we analyzed the correlation between hs-CRP with p-p65, p-IκBa and TF protein expression in experimental groups. Results:Thrombosis was not found in the heart and blood vessels. The level of hs-CRP and blood routine in experimental groups were obviously higher than those in control group, the difference was statistically significant (P<0.05). The structure of lung were normal in control group and Casein group; while lots of inflammatory cells infiltrated in the alveolar wall in SP group and PA group. The level of D-dimer in experimental groups were obviously higher than that in control group, the difference was statistically significant (P<0.05). Compared with control group, the experimental groups had massive increased in the mRNA expression of NF-κB p65 and TF, protein expression of p-p65, p-IκBa and TF, the difference was statistically significant (P<0.05). There were positive correlations between hs-CRP with p-p65, p-IκBa and TF protein expression. Conclusion:TF as a promoter of coagulation system, mediated by NF-JB under inflammation stress. With the strengthen of inflammation, the coagulation function was enhanced. Inflammation, especially the infection was strongly associated with TF expression mediated by activated NF-κB pathway. It was more capable to mediate TF expression in PA group than that in SP group, when the hs-CRP level had no obviously difference.