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

Objective: To investigate the rules of change in lung substance P (SP)and TNF-a during severe acute pancreatitis(SAP)–associated lung injury (PALI) . To observe the action of Qingyitang on lung SP level so as to excavate the therapeutic action of traditional Chinese drug Qingyitang in PALI.Methods: SAP model was induced by retrograde infusion of 1.5% sodium deoxycholate into biliopancreatic duct of Spraghe-Dawley rats. 120 healthy Spraghe-Dawley rats (220g-280g) were randomly divided into 4 groups. Group I was treated with sham operation; Group II undergone SAP surgery but without any treatment; Group III with SAP surgery were treated with Spantide through caudalis vein intubation and Group IV with Qingyitang by intragastric administration. Every 8 rats were disposed to observation in each group after corresponding treatment after 6 hours, 12 hours and 24 hours, respectively Serum amylase (AMY ) and myeloperoxidase (MPO) of lung was determined by biochemical method.The level of SP and TNF-a in lung were measured by enzyme linked immunosorbent assay(ELISA) at the same time. Wet/dry weight ratio of lung were calculated . Histopathological changes of Lung were observed under light microscope. immunohistochemistry technique were used to detect the expression of protein levels of Aquaporin1(AQP1) and leves of neurokinin-1 receptor( NK-1R) in lung, respectively.Results: (1) Compared with sham operation groups,the levels of serum AMY, SP and TNF-a and MPO of lung in SAP groups increased respectively in a time-dependent manner (P<0.01,P<0.01,P<0.01,P<0.01 ), Wet/dry weight ratio of lung increased markedly (P<0.01). The pathologic changes of lung in SAP group were edema and congestive with 1arge of neutrial cells infiltration . Atelectasis could be observed locally . Immuno- histochemistry revealed that moderate to strong NK-1R immunoreactivity was localized to alveolar membrane,I,II epithelium and polymorphonuclear leukocytes in the lung of SAP. The expression of AQP1 decreased significantly and NK-1R increased in SAP groups time depedently compared with that of sham operation groups(P<0.05 ,P<0.05). (2) After treatment with Spantide or Qingyitang, levels of serum AMY , SP and TNF-a and MPO of lung decreased (P<0.01 ,P<0.01 ,P<0.01 ,P<0.01 ) , ascites amount and Wet/dry weight ratio of lung decreased markedly (P<0.01), the expression of AQP1 increased and NK-1R decreased (P<0.05, P<0.05).Pathophysiologic changes in lung relieved significantly.The diference were apparente between Spantide and Qingyitang group (p<0.05),but the expression of AQP1 and NK-1R was no diference between them(P>0.05 ,P>0.05). (3) Statistical analysis revealed correlation between substance P and TNF-a(0< r<1,P < 0.05).Conclusions: In SAP, neurokinin-1 receptor antagonist(spantide) combined with substance P, exerting a beneficial effect on acute lung injury through blocking substance P, has a therapeutic effect on the disease. Qingyitang may exerts its treated effect on lung injury by reducing the level of substance P in lung .