| ObjectiveTo research the influence of TREM-1 to inflammation induced by LPS (cellular level and animal model), and the effect of it to pathogen clearnce in sepsis model; and to research the accommodation of azithromycin to TREM-1.Mothods1. The THP-1 cells were cultivated and were separated from three groups: LPS group, LPS+ TREM-1/Fc fasion protein group and LPS+ azithromycin group. The cells and supernate were collected in 4h, 8h, 12h, 24h and 48h. The concentration of inflammation cytokine (sTREM-1, TNF-α, IL-6 and IL-1β) were detected by ELISA. The protein expression of TREM-1 were measured by flow cytometer and western blot. The gene expression of it were detected by RT- PCR. 2. In LPS animal model, male S/D rats were separated from three groups: control group, azithromycin group and TREM-1/Fc fasion protein group. The live time, survival number and survival state were objected (action, mental status and eating) . The blood were drawed through tail vein every day, and the concentration of inflammation cytokine (sTREM-1, TNF-α, IL-6 and IL-1β) were detected by ELISA. At the third day, the rats were killed and their lung were handled by macropathology and HE stain in order to study the inflammation degree. 3. In Pseudomonas aeruginosa model, the rats were separated from control group and TREM-1/Fc fasion protein group. At the third day, the rats were killed and their lung tissue were grinded with liquid nitrogen. After centrifugation in low velocity, the bacterial number of supernate were mensured by MTT. The bacteria of supernate were cultivated in blood agar culture-medium and were identified.Result1. The protein expression of TREM-1 under LPS were inhibited by TREM-1/Fc fasion protein and azithromycin by flow cytometer and western blot, but the gene expression couldn't be affected. The secretion of inflammation cytokine were inhibited by them, compeared with the LPS group, the concentration of inflammation cytokine were descended specially ( P<0.01), and the effect of the former was stronger than of the azithromycin group, including sTREM-1 ( P<0.01), TNF-α, IL-1βand IL-6(P<0.05). 2. In LPS rats models, the survival rate was highest is in the TREM-1/Fc fasion protein group, followed by azithromycin group. There was 26 hours of survival time, 100% mortality and 0% survival rate in the LPS group; 52.3% survival rate in the TREM-1/Fc fasion protein group and 31.3% survival rate in the azithromycin group. The secretion of inflammation cytokine were inhibited by them and the effect of the former was stronger, including sTREM-1 and TNF-α(P<0.01), IL-6 and IL-1β( P<0.05). In the pathology of lung tissues, the inflammation injuries were better in TREM-1/Fc fasion protein group and azithromycin group than control group, especially the former. In the LPS group, there were a lot of inflammation cells infiltrated and assembled into lung interstitial tissue, the alveolar wall thickened and the normal structure was bronken. In the azithromycin group, there were some inflammation cells in interstitial tissue, the structure was fairly normal and a part of the alveolar wall were broken. In the TREM-1/Fc fasion protein group, there were a little of inflammation cells infiltrated and the tissue stracture was normal. 3. In Pseudomonas aeruginosa model, the survival rate was higher of the TREM-1/Fc fasion protein group than the control group. There was 16 hours of the shortest life time and 43.6% survival rate in the former, compaired with 10 hours and 12.5% survival rate in the latter. There were no normal stracture and many inflammation cell infiltrated into interstitial tissue in the control group, but there were some inflammation cells in interstitial tissue, the alveolar wall were thickened partly and the structure maintained integrated. The pathogen burden was less in the TREM-1/Fc fasion protein group.Conclusion The inflammtion reaction induced by LPS could be control by TREM-1, which could reduce the secretion of inflammtory factors. Through controlling TREM-1, the the survival rate were improved, the inflammation reaction of lung were reduced. The antibacterial functions was remained partily and the pathogen burden of the tissue were less by TREM-1 being inhibited. So TREM-1 was a ideal inflammation reporter. Azithromycin could partily inhibited the expression of TREM-1 under LPS, decreased the releasing of the inflammation factors, elevated survial rate and relieved the inflammation of lung in LPS rats. It had been used for long time in clinical application and had a little of side effect, so it was a good choice in immunoregulant.
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