Mechanism of short chain fatty acids on immunomodulatory effects in rats with bronchiectasis
OBJECTIVE To explore the immunomodulatory mechanism of short chain fatty acids(SCFAs)on the bronchiectasis model rats induced by pseudomonas aeruginosa(PA).METHODS Twenty SPF grade rats were randomly divided into control group,model group,SCFAs low-dose and high-dose groups.The rat model of bronchiectasis was established by endotracheal injection of 0.5 mL of 10-128 CFU/mL PA.The rats in the SCFAs low-dose and high-dose groups were given 100 mg/kg and 150 mg/kg SCFAs mixture(the ratio of acetic acid,propionic acid and butyric acid was 3∶1∶1)daily by intragastric administration,respectively,while the rats in the control group and model group were given 10 mL/(kg·d)normal saline by intragastric administration,for 7 consecutive days.HE staining was performed on lung tissues of each group.The levels of NF-κB,GM-CSF,IL-17A and IL-22 in the serum were detected by ELISA.The expressions of STAT3,STAT5 and TLR2 in lung tissues were detected by Western blot.RESULTS In the model group,the bronchial lumen was dilated and deformed,the tube wall was thickened,a large number of inflammatory cells were infiltrated around the bronchial tube,and fibrous tissues were formed.The bronchial deformation was recovered in the SCFAs low-dose and high-dose groups,the inflammatory cells infiltration and fibrous tissue were significantly reduced,and the improvement was more obvious in the high-dose group.Compared with the model group,the levels of NF-κB,GM-CSF,IL-17A and IL-22 in the SCFAs low-dose and high-dose groups were significantly increased(P<0.05),and the levels in high-dose group were more significant increased.Compared with the model group,the expressions of STAT3 and TLR2 were not significantly changed in the SCFAs low-dose and high-dose groups,while the expression of STAT5 was significantly decreased(P<0.05).There was no statistical significance between low-dose group and high-dose group(P>0.05).CONCLUSIONS SCFAs can promote the secretion of inflammatory factors and play an immunomodulatory role in the acute infection period of PA-induced bronchiectasis model rats,and its mechanism might be related to TLR2/NF-κB/STAT signal pathway.