Role Of PPAR-γ In Acute Pancreatitis And Pancreatitis-associated Lung Injury And The Effect Of Chinese Medicine Qingyitang

Objective:By investigating the role of PPAR (peroxisome proliferator-activated receptor) y and its ligands in severe acute pancreatitis (SAP) associated lung injury in this experiment, we provide new ideas and treatment methods to control SAP associated lung injury, and we further explain the mechanism of Chinese medicine Qingyitang treatment of acute pancreatitis. So we offered new clues and inspiration to extract active ingredients from the traditional Chinese medicine and to research the traditional Chinese medicine.Methods:60 healthy male Wistar rats, weighing 220-280g, were randomly divided into six groups:the sham group, SAP group (model group), PPARy ligand rosiglitazone (ROSI) treatment group, PPARy antagonist GW9662 treatment group, traditional Chinese medicine Qing Yi Tang treatment group, PPARy antagonist GW9662+Qing Yi Tang treatment group, n=10. SAP Group:retrograde cholangiopancreatography injected 1.5% sodium deoxycholate (0.1 ml/100 g)to establish the model of SAP associated lung injury, jugular vein cannulation and injection of normal saline 2 ml/kg, and then rats can drink water freely but food is forbidden; sham operation group:only slightly flips the pancreas after abdominal laparotomy, not retrograde cholangiopancreatography injected and the other operations is the same with the SAP group; PPARy ligands Group: After the modeling 10 minutes, the external jugular vein injection of rosiglitazone (ROSI),0.3 mg/kg (dissolved in 10% DMSO), the other operations is the same with the SAP group; PPARy antagonist treatment group:After the modeling 10 minutes,the external jugular vein injection of GW9662 (0.3mg/kg).After the second 10 minutes neck vein injection of rosiglitazone (0.3 mg/kg),the other operations is the same with the SAP group; traditional Chinese medicine treatment group:intragastric administration by using Qingyitang immediately after the modeling,dose of 1ml/100g,and the other operations is the same with the SAP group; PPAR/y antagonist+medicine treatments:intragastric administration by using Qingyitang immediately after the modeling,the dose is the same with the above group.10 minutes later, the external jugular vein injection of GW9662 (0.3mg/kg), the other operations is the same with the SAP group All the animals were killed after 6h, and blood specimens were used for detecting the serum amylase, PO2, PCO2, endotoxin was detected by tachypleus amebocyte lysate, TNF-a was measured by radioimmunoassay, take the right upper lobe measuring wet/dry ratio, right lower lobe using RT-PCR method to measure the CINC (cytokine-induced neutrophil chemoattractant) mRNA, the remaining right lung as a pathological observation, measuring the left lung CINC-1 levels with the ELISA method.Results:(1)SAP model group compared with sham group:serum amylase, PCO2, endotoxin,TNF-a, wet/dry ratio, CINC content increased significantly (P<0.05), PO2 decreased significantly (P<0.05), CINC mRNA expression increased(P<0.05),lung tissue appeared congestion,edema, infiltration of neutrophils and focal atelectasis and other changes.(2) PPARy ligand group compared with the SAP model group:serum amylase, PCO2, endotoxin,TNF-a,wet/dry ratio,CINC-1 levels decreased significantly (P <0.05), PO2 recovered significantly (P< 0.05), CINC mRNA expression was reduced (P<0.05), the pathological changes of lung tissue reduced significantly. (3) PPARy antagonist treatment group compared with the SAP model group:serum amylase, PO2, PCO2, endotoxin, TNF-a, wet/dry ratio, CINC-1 content, CINC mRNA expression showed no significant difference (P> 0.05), and there is no obvious pathological changes in lung tissue changes,too. (4) Chinese medicine treatment group compared with the SAP model group:serum amylase, PCO2, endotoxin, TNF-a, wet/dry ratio, CINC-1 was significantly decreased (P<0.05), PO2 rebounded significantly (P<0.05), CINC mRNA expression was reduced(P<0.05), the lung pathological changes reduced significantly.(5) PPARy antagonists+Chinese medicine treatment group compared with the Chinese medicine treatment: serum amylase, PCO2, endotoxin, TNF-a, wet/dry ratio, CINC-1 levels rebounded (P<0.05), PO2 are decreased (P<0.05), CINC mRNA expression increased(P<0.05), pathological changes in lung tissue increased.Conclusions:(1)application of 1.5% sodium deoxycholate retrograde cholangiopancreatography injection,the rat lungs had congestion, edema, inflammatory cell infiltration, focal atelectasis and other changes, and this indicated that the prepared SAP associated lung injury model is successful. (2) PPARy ligand activation of PPARy, the enable SAP induced lung injury is reduced significantly significant improvement in the indicators,and the effect can be reversed by PPAR-y antagonist, thus confirming PPARy and its ligand on SAP associated lung injury in a protective role. (3) Qingyitang is an effective prescription to treat the SAP associated lung injury, its mechanism of the treatment of SAP-associated lung injury,to some extent, directly or indirectly through the activation of PPARy and play the role of agonist ligand.