Ulinastatin alleviates pulmonary edema by reducing pulmonary permeability and stimulating alveolar fluid clearance in a rat model of acute lung injury

Objective(s): Previous studies have shown that ulinastatin (UTI) alleviates pulmonary edema in acute lung injury (ALI) caused by lipopolysaccharide (LPS), although the mechanism behind this action is uncertain. This research aimed to identify the fundamental mechanism by which UTI alleviates pulmonary edema.Materials and Methods: We established a model of acute lung injury (ALI) in rats by using LPS as the inciting agent.The control, LPS, and LPS+UTI groups were each comprised of a specific number of randomly selected Wistar rats. We evaluated lung injury and determined pulmonary edema. The concentrations of TNF-α, IL-۱β and IL-۶ in BALF and the expression levels of α۱Na, k-ATPase, β۱Na, K-AtPase, α-ENaC, β-ENaC, γ-ENaC, Zonula occludens (ZO)-۱, Occludin, Caludin-۵, PI۳K, Akt, TLR۴, MyD۸۸ and NF-ƘBwere identified in lung tissues.Results: The presence of UTI was associated with a reduction in lung pathological alterations, lung injury scores, the lung W/D ratio, and MPO activity, in addition to the improved gas exchange (P<۰.۰۱). Furthermore, UTI alleviated EB leakage and stimulated AFC (P<۰.۰۱). Importantly, UTI increased the expression of ZO-۱, Occludin, Caludin-۵, α۱Na, K-ATPase, β۱Na, K-AtPase, α-ENaC, β-ENaC, and γ-ENaC (P<۰.۰۱). Furthermore, UTI inhibited the inflammatory response, enhanced the expression of PI۳K and Akt and hindered TLR۴, MyD۸۸, and NF-ƘB expression (P<۰.۰۱) in lung tissues.Conclusion: Our results demonstrated that UTI attenuated pulmonary edema by reducing pulmonary permeability and promoting AFC through inhibiting the inflammatory response, and the mechanism is related to promoting PI۳K/Akt signaling pathways and suppressing TLR۴/MyD۸۸/NF-ƘB signaling pathways.

کلیدواژه ها:

Acute lung injury ، Epithelial sodium channel ، K-ATPases ، Na ، Pulmonary edema ، Tight junction proteins ، Ulinastatin