The Mechanism Underlying Alpinetin-mediated Alleviation Of Pancreatitis-associated Lung Injury Through Upregulating Aquaporin 1

Objective: An investigation into the alpinia katsumadai hayata extract flavonoids-Alpinetin effects on lung injury caused by acute severe pancreatitis, explore the alpinetin relieve acute lung injury degree of concrete mechanism. Methods : In vivo tests using knockout mice and normal rat pancreatic lung injury model was established, in vitro experimental model is established in this paper is the application concentration of 0.01 mg/l, 0.1 mg/l, 1.0 mg/l, 10 mg/l LPS effect on pulmonary microvascular endothelial cells, induced acute lung microvascular endothelial cell damage model, after the success of the model in vivo and in vitro based application of different concentrations of alpinetin effects on lung injury model, alpinetin on severe acute pancreatitis complicated with lung injury of protection. Using immunohistochemistry and Western blot, RT-PCR, and determined by MTT method to detect the acute pulmonary microvascular endothelial cell injury induced by LPS model human lung microvascular endothelial cell survival rate and lung tissues and cells in animal model of TNF alpha and AQP 1(water channel protein- 1) expression changes. Application concentration of 0.01 mg/l respectively, and 0.1 mg/l, 1.0 mg/l, 10 mg/l LPS effect on pulmonary microvascular endothelial cells, induced acute lung microvascular endothelial cell damage model, and applies the concentration of 40 mg/l, 80 mg/l, 160 mg/l alpinetin role in pulmonary microvascular endothelial damage model induced by LPS, observe alpinetin protective effect on pulmonary microvascular endothelial cells. Using Western blot, RT-PCR, and determined by MTT method to detect the acute pulmonary microvascular endothelial cell injury induced by LPS model the survival of the human lung microvascular endothelial cells and the TNF-α and AQP-1(water channel protein-1) expression changes. Results: After LPS induced pulmonary microvascular endothelial cells and animal model of TNF alpha protein expression in lung tissue damage increase obviously, and the expression of AQP-1 drop, respectively, with different concentrations of alpinetin effects on pulmonary microvascular endothelial damage model induced by LPS and lung tissue injury animal model, the expression of TNF alpha protein significantly suppressed compared with model group(p<0.05).The AQP-1 mRNA and protein expression increased significantly. Conclusions: Overall, our study shows that alpinetin alleviates SAP-induced ALI. The likely molecular mechanism includes upregulated AQP expression, which inhibits TNF-α and thus, alleviates SAP-induced ALI.