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

Jiang, Yuan-xu1; Huang, Ze-wei2

2022-08-01

10.22038/IJBMS.2022.64655.14230

Iranian Journal of Basic Medical Sciences   Impact Factor & Quartile

2008-3866

2008-3874

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-alpha, IL-10 and IL-6 in BALF and the expression levels of alpha 1Na, k-ATPase, 01Na, K-AtPase, alpha-ENaC, 0-ENaC, gamma-ENaC, Zonula occludens (ZO)-1, Occludin, Caludin-5, PI3K, Akt, TLR4, MyD88 and NF-KBwere 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<0.01). Furthermore, UTI alleviated EB leakage and stimulated AFC (P<0.01). Importantly, UTI increased the expression of ZO-1, Occludin, Caludin-5, alpha 1Na, K-ATPase, 01Na, K-AtPase, alpha-ENaC, 0-ENaC, and gamma-ENaC (P<0.01). Furthermore, UTI inhibited the inflammatory response, enhanced the expression of PI3K and Akt and hindered TLR4, MyD88, and NF-KB expression (P<0.01) 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 PI3K/Akt signaling pathways and suppressing TLR4/MyD88/NF-KB signaling pathways.

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

SCI

English

First ; Corresponding

Shenzhen Key Medical Discipline Construction Fund[SZXK044] ; Sanming Project of Medicine in Shenzhen[SZSM202011021]

Research & Experimental Medicine ; Pharmacology & Pharmacy

Medicine, Research & Experimental ; Pharmacology & Pharmacy

WOS:000844170200007

MASHHAD UNIV MED SCIENCES

Web of Science

1.Southern Univ Sci & Technol, Jinan Univ, Affiliated Hosp 1, Clin Med Coll 2,Shenzhen Peoples Hosp,Dept Anesth, Shenzhen 518020, Guangdong, Peoples R China
2.Shenzhen Peoples Hosp, Dept Crit Care Med, Shenzhen 518020, Guangdong, Peoples R China

Jiang, Yuan-xu,Huang, Ze-wei. Ulinastatin alleviates pulmonary edema by reducing pulmonary permeability and stimulating alveolar fluid clearance in a rat model of acute lung injury[J]. Iranian Journal of Basic Medical Sciences,2022,25(8).

Jiang, Yuan-xu,&Huang, Ze-wei.(2022).Ulinastatin alleviates pulmonary edema by reducing pulmonary permeability and stimulating alveolar fluid clearance in a rat model of acute lung injury.Iranian Journal of Basic Medical Sciences,25(8).

Jiang, Yuan-xu,et al."Ulinastatin alleviates pulmonary edema by reducing pulmonary permeability and stimulating alveolar fluid clearance in a rat model of acute lung injury".Iranian Journal of Basic Medical Sciences 25.8(2022).