Protective effect of Ulinastatin on acute lung injury in diabetic sepsis rats
Zhe Jin, Mengyun Li, Li‐Juan Tang, Yufeng Zou, Kai Chen
Abstract
This study explored the protective effect and its possible mechanism of ulinastatin (UTI) on acute lung injury (ALI) in type 2 diabetes mellitus (DM) sepsis rats. Following treatment with UTI, the wet/dry weight (W/D) ratio, pathological changes, hypoxia-inducible factor-1ɑlpha (HIF-1ɑ) protein and Toll-like receptor 4 (TLR4) mRNA expression of lung tissues, the expression levels of interleukin-1beta (IL-1ß), IL-18, and tumor necrosis factor-alpha (TNF-ɑ), the contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in serum were detected in type 2 DM sepsis rats. It was found that rats with type 2 DM and sepsis showed obvious damage in lung tissues with significantly increased inflammatory cells, necrosis, and swelling of alveolar epithelial cells, but UTI decreased the lung damage induced by DM and sepsis. In addition, compared with the control, the W/D ratio, serum IL-1ß, IL-18 and TNF-ɑ contents, HIF-1ɑ protein expression, TLR4 mRNA expression, pulmonary microvascular permeability, MDA content in serum in type 2 DM and sepsis groups were significantly increased in type 2 DM sepsis rats (p < 0.05). However, compared with the groups with type 2 DM sepsis, the W/D ratio, serum IL-1ß, IL-18, TNF-ɑ contents, HIF-1ɑ protein expression, TLR4 mRNA expression, and pulmonary microvascular permeability in UTI-treated group were significantly decreased, but the activity of SOD increased (p < 0.05). This study indicates that UTI can effectively reduce ALI induced by diabetic sepsis in rats through inhibiting inflammatory response, reducing oxidative stress, regulating hypoxia response pathway, and improving pulmonary microvascular permeability.