Tetramethylpyrazine Protects Obese Rats From Lung Injury By Affecting PBEF-NF-?B Pathway

Objective: To investigated the effects of Pre-B-cell colony-enhancing factor(PBEF)on the development of Acute respiratory distress syndrome(ARDS)in obese models,and explored the protective effects of tetramethylpyrazine(TMP)on ARDS obese models as well as underlying mechanism.Method: 48 healthy male SD rats were randomly divided into 6 groups: control group,ARDS group,obese group,obese ARDS group,obese + tetramethylpyrazine group and obese ARDS + tetramethylpyrazine group.Obese rats were fed with high-fat diet and normal rats were fed with normal diet.The obese model was successfully established when the average body weight was more than 20% in the control group.At this time,ARDS rats were injected with lipopolysaccharide(LPS),The other two groups were injected with the same amount of saline.8 hours later,the rats were sacrificed to take abdominal aorta blood and blood gas analysis.At the same time,rats were thoracotomy to take lung to detect wet/dry(W/D)weight ratio.The pathological changes of lung tissue were observed after hematoxylin-eosin(HE)staining.Real-time quantitative reverse transcription-polymerase(RT-PCR)was used to detect the expression of PBEF mRNA.The expression level of PBEF protein,NF-?B p65 submit and NF-?B p-p65 subunit were detected by Western Blot.The positive expression of PBEF was detected by immunohistochemistry.Results: The fat model was successfully established in the sixth week of high fat diet.Blood gas analysis showed that arterial oxygen pressure was significantly decreased in ARDS group and obese ARDS group,and the degree of arterial oxygen pressure reduction was more serious in obese ARDS group,the lung W / D value of normal control group,obese group,ARDS ARDS group and obesity group increased in turn,While W / D values were decreased after intervention with tetramethylpyrazine in obese and obese ARDS rats.HE staining showed that the lung tissue was normal in the control group.The alveolar septum was thickened and the infiltration of inflammatory cells was observed in the obese group.The alveolar septum of the ARDS group was thickened and the erythrocyte infiltration was found in the alveolar cavity.obese ARDS group,the degree of pulmonary inflammation is the most obvious,alveolar cavity can be seen a large number of exudate,red blood cells and inflammatory cells.obesity + TMP group no obvious alveolar septal thickening,obese ARDS + TMP group no obvious oozing and cell infiltration.The severity of lung injury in obese and obese ARDS rats was heavier than that in control groups,it was found that the level of body mass in rats was correlated with the severity of ARDS.And tetramethylpyrazine for obese rats and obese ARDS rats have a certain lung protection.Detection by RT-PCR and WB,it was found the expression of PBEF mRNA and protein in lung tissue of normal control group,obese group,ARDS group and obese ARDS group were increased in turn,and the expression of PBEF mRNA and protein in lung tissue of obese group and obese ARDS group decreased after TMP intervention.At the same time,through the WB can be found the expression of NF-?B p65 submit and NF-?B p-p65 submit in lung tissue of normal control group,obese group,ARDS group and obese ARDS group were increased in turn,and the expression of NF-?B p65 submit and NF-?B p-p65 submit in lung tissue of obese group and obese ARDS group decreased after TMP intervention.By immunohistochemistry,we found that the control group lung tissue almost no expression PBEF;obese alveolar epithelial cells with a small amount PBEF expression;expression ARDS alveolar epithelial cells PBEF increased significantly;there was a strong positive reaction in alveolar wall and alveolar exudates of lungs of obese ARDS group;obesity + TMP group showed a small amount of alveolar epithelial cells PBEF expression,The expression of PBEF in lung epithelial cells of obese ARDS + TMP group was significantly lower than that of obese ARDS group.It was found that the expression level of PBEF-NF-?B pathway increased with the increase of body mass level and severity of lung injury.PBEF-NF-?B pathway may be involved in the development and progression of ARDS in obese rats.After the administration of tetramethylpyrazine,the expression of PBEF-NF-?B pathway is decreased,suggesting that tetramethylpyrazine has an inhibitory effect on this pathwayConclusion: The level of body mass in rats was correlated with the severity of ARDS.Obesity may be an independent risk factor for lung injury.The level of PBEF-NF-?B pathway was increased with the increase of the degree of obesity,and the expression level of PBEF-NF-?B pathway increased with the increase of lung injury severity,PBEF-NF-?B pathway may be one of the mechanisms of obesity aggravating the severity of lung injury.tetramethylpyrazine has lung protection for obese rats and obese ARDS rats,its possible mechanism is to inhibit PBEF-NF-?B pathway.