Role Of PBEF In Acute Pancreatitis And Pancreatitis-associated Lung Injury And The Effect Of QingYiTang

Objective:To observe the expression and function of pre-B cell cloning factor (PBEF) of the rat's blood and lung tissue in severe acute pancreatitis (SAP) associated acute lung injury (ALI) model, and the effects of Qingyitang on PBEF expression. To reveal a new perspective pathogenesis of severe acute pancreatitis associated with lung injury.Chinese medicine Qingyitang is used and the results may give us some new ideas for severe acute pancreatitis treatment.Methods:One hundred and fortyfour health Spraghe-Dawley (SD) rats weight (200-220) g, male, were randomly divided into 6 groups (SAP model group, Sham operation group, and Dexamethasone group, Linglanxin group, Sandostatin group, Qing Yitang group). These 24 animals in each group were randomly divided into Oh,6h,12h,24h subgroup,8 rats were at each subgroup. All modles were induced by retrograde infusion of 1.5% sodium deoxycholate (1 ml/kg) into biliopancreatic duct of Spraghe-Dawley rats except sham operation group. Dexamethasone group, Sandostatin group, Linglanxin group were done with intravenous injection immediately after modeling the first and 12h once again, respectively intravenous dose: 1 ml/kg,20μg/kg,2mg/kg. Qingyitang was given in Qingyitang group with gastric canal injection immediately after modeling the first and 12h in dose:10ml/kg. In Sham group, the pancreas was only flipped after laparotomy. All the rats were sacrificed at 6 h,12 h,24 h respectively after operation, the lung tissue and arterial and venous blood were taken off for pathological examination and some indexes measurement. The level of PBEF in lung was measured by enzyme linked immunosorbent assay(ELISA),the expression and location of PBEF were measured by immunohistochemistry. RT-PCR technique was used to detect the expression of mRNA levels of PBEF and Western Blotting was used to detect the expression of protein levels of PBEF, respectively. Quantitative chromogenic tachypleus amebocyte was used to detect the endotoxin. TNF-α, IL-1βand IL-8 were measured by radioimmunoassay respectively. Wet/dry weight ratio of lung were calculated. Blood gas analysis and serum amylase (AMY) was determined by biochemical method. Histopathological changes in lung were observed under light microscope.Results:The expression of PBEF mRNA and protein in lung tissue, the levels of serum PBEF, TNF-α, IL-1β, IL-8, endotoxin,amyIase, lung W/D ratio, PaCO2 in arterial blood of model group were significantly higher in the same point than those of sham operated control group, meanwhile PaO2 in arterial blood decreased significantly (p<0.01). Some other indexes of ALI showed obvious pathogenic changes in model group and so did the pathogenic examination of lung tissue. Qingyitang Dexamethasone, Santonstadine could decrease the levels of serum PBEF, the expression of PBEF mRNA and its protein in lung tissue, eliminate the extent of lung injury, but Linglanxin could not do that well.The decline of endotoxin, TNF-α, IL-1β, IL-8 in Qingyitang group was more significant(p<0.05). Santonstadine could reduce amylase content obviously. And Dexamethasone showed superiority in ameliorating lung W/D ratio,PaCO2 and PaO2.Conclusions:Infusion of 1.5% sodium deoxycholate into biliopancreatic duct of Spraghe-Dawley rats, the pathologic changes of lung were edema and congestive with large of neutrial cells infiltration and focal atelectasis, the levels of serum AMY, PaCO2 and W/D increased obviously, meanwhile PaO2 decreased significantly. All indexes showed that the APALI model is welldone.During acute lung injury induced by severe acute pancreatitis, many factors have very important effects on pathogenisis of ALI, such as elevated level of endotoxin,overexpression of PBEF which activated overexpression of TNF-a, IL-1β, IL-8.Qingyitang could exert protecting effects through decreasing PBEF expression,reducing the excessive activation of alveolar macrophages, expression of TNF-a, IL-1βand IL-8 in a large number of inflammatory factors, aggregation of PMN, the level of serum endotoxin and amylase and decreasing alveolar permeability and other aspects of mechanism.Dexamethasone and Santonstadine could play their available role in ALI by eliminating PBEF of different levels. Both of them could impact different indicators through different ways.The effects of Chinese and Western medicines on SAP were related to different aspects of the pathogenesis of ALI, and play an important role by their own strengths. Combining Chinese and Western medicine under the guidance of the integration of traditional and western medicine theory, will provide a new effective way to prevent and cure SAP and SAP associated ALI in clinic.