Significance Of PPAR-γ And ANGPTL4in Pathogenesis Of Severe Acute Pancreatitis-associated Lung Injury And Studies About Regulatory Effects Of Chinese Medicine Qingyitang Decoction

Objectives: To investigate the potential role of peroxisome proliferator-activatedreceptor-γ (PPAR-γ) and angiopoietin-like protein4(Angptl4) in pathogenesis of severeacute pancreatitis–associated lung injury, and study the mechanism of treatmentaleffects about traditional Chinese medicine Qingyitang decoction and Dexamethasone.Aimed to provide experimental evidences for treating severe acute pancreatitis–associated lung injury and looking for more feasible drug-effecting targets.Methods: Severe acute pancreatitis-associated lung injury rat model wasestablished by retrograde injection of different concentration of sodiumdeoxycholate(1.5%) into the common biliopancreatic duct. Fifty-six male healthy SPFlevel Spraghe-Dawley rats (180g-220g) were divided into7groups randomly with8ratsof each group. Group I (sham operation), Group II(SAP), and5treatment groups:Group III(SAP+GW9662,5mg/kg), Group IV(SAP+Rosiglitazone,5mg/kg), Group V(SAP+Dexamethasone,10mg/kg), Group VI(SAP+Qingyitang decoction,5mg/kg),Group VII(SAP+Dexamethasone,10mg/kg+Qingyitang decoction,5mg/kg). Every8rats were disposed and observed in each group. All the rats were killed at24hours afteroperation. Blood and lung tissue was collected.The pathological alterations of lung tissue and pancreas tissue were observed underlight microscope. Serum amylase (AMY) and SPO2were both determined bybiochemical method. The ratio between Wet and Dry weight of lung tissue was calculated by vacuum drying method. The level of TNF-α in blood was measured byELISA. At the same time, the levels of PPAR-γ and Angptl4mRNA in lung tissue wasanalyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and theexpression of protein levels of PPAR-γ and Angptl4was detected by Western-Blot.Results: The levels of serum TNF-α, AMY and the W/D ratio of lung tissue andthe expression of Angptl4mRNA and protein in lung tissue in SAP group weresignificantly higher in the same index than those in the sham operation group, while theexpression of PPAR-γ mRNA and protein in lung tissue in SAP group were lower thanthose in the sham operation group (P<0.01). Those indexes in QingYiTang decoctiongroup, Dexamethasone group and the syndicate group were significantly lower thanthose in SAP group, at the same time the level of expression of PPAR-γ mRNA andprotein in lung tissue is reversed(P<0.01). The expression level of Angptl4and PPAR-γmRNA and protein in lung tissue in Rosiglitazone group was higher than those in SAPgroup, while the situation in GW9662groupe was reversed(P<0.01).Conclusions: In pathogenesis of acute lung injury induced by severe acutepancreatitis, The overexpression of Angptl4and the inhibition of PPAR-γ may playimportant protection roles. Dexamethasone can decrease the release of the mediatorsand cytokines of inflammation. In addition, Chinese medicine Qingyitan can attenuateacute lung injury induced by SAP. Combined traditional Chinese medicine and Westernmedicine can play complementary roles of improving pulmonary function...