基于TLR4/MyD88/NF-κB通路探讨乌司他丁减轻脂多糖诱导的大鼠急性肺损伤的作用

doi:10.3969/j.issn.1006-6233.2019.08.018

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Abstract Objective: To observe the ulinastatin on acute lung injury induced by lipopolysaccharide in mice protection and of TLR4/MyD88/NF-κB signaling pathway. Methods: 48 SPF Wistar male rats aged 12-15 weeks were randomly divided into four groups. The acute lung injury (ALI) model was established by intravenous injection of 0.5mL lipopolysaccharide (LPS) (5mg/kg) into the tail of the model group. The control group was given saline of equal volume. The dexamethasone (DXM) intervention group and ulinastatin (UTI) intervention group were given intraperitoneal injection of 1 mL dexamethasone (2 mg/kg) and 1 mL dexamethasone (1 mL) 24 hours and 10 minutes before LPS injection, respectively. UTI solution (5 mg/kg) was pretreated, while the control group and the model group were given saline of equal volume instead. The weight loss ratio and wet-dry weight ratio (W/D) of lung tissue were calculated for 10 hours. Pulmonary vascular endothelial permeability was measured by Evanslan method. Lung pathological changes were observed by hematoxylin-eosin staining (HE) and scored. The levels of TNF-alpha, IL-6 and IL-1 beta in bronchial lavage fluid (BALF) were detected by ELISA. The number of total cells and neutrophils was observed and counted under microscope. The expression of TLR4, MyD88 and NF-kappa B proteins in TLR4/MyD88/NF-kappa B signaling pathway was detected by Western blot. Results: Compared with control group, model group and DXM intervention group rats weight and UTI intervention group were obviously decreased (P<0.05), compared with model group, DXM intervention group and UTI intervention group obviously increased (P<0.05). Compared with control group, model group rats after by LPS stimulation, W/D ratio increased significantly (P<0.05); Compared with model group, DXM intervention group and UTI intervention group W/D ratio significantly decreased (P<0.05). Compared with control group, model group appeared the number of neutrophil and total cells in BALF significantly increased (P<0.05); Compared with model group, DXM group and ulinastatin group the number of neutrophil and total cells in BALF of obvious declined(P<0.05).Compared with control group, model group rats with Evans blue concentration appear obviously increased (P<0.05), compared with model group and DXM group and UTI group rats Evans blue concentration significantly decline, statistically significant difference (P<0.05). The control structure of lung tissue integrity, no congestion, the alveolar cavity was clear, interval found no edema and inflammatory cell infiltration. Compared with control group, the mo new alveolar cavity decreased significantly, interval appeared thickened, alveolar walls appeared hyperemia and edema, and found a lot of inflammatory cells infiltration, HE score significantly higher than the control group (P<0.05). And DXM group, ulinastatin group compared with model group, was close to normal lung tissue structure, inflammatory cells infiltration, DXM group and ulinastatin group HE scores significantly lower than the model group, the difference was statistically significant (P<0.05). Compared with control group, model group of IL-6 and IL-1,TNF-αlevel appear obviously increased (P<0.05); Compared with model group and DXM group and ulinastatin group rat BALF of IL-6 and IL-1, TNF-αlevel appear obvious dropped, statistically significant difference (P<0.05). Compared with control group, model group of TLR4, MyD88, NF-κB protein expression increased significantly (P<0.05); Compared with model group, TLR4, MyD88, NF-κB protein expression in DXM group and ulinastatin group decreased obviously, statistically significant difference (P<0.05). Conclusion: Ulinastatin can inhibit the activation of TLR4/MyD88/NF-kappa B signaling pathway induced by LPS, thereby alleviating inflammatory response and exerting protective effect on LPS-induced lung injury.

Key words： Ulinastatin Acute lung injury Lipopolysaccharide TLR4 MyD88 NF-κB

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WANG Xi,MU Qiantu,et al. Effect of Ulinastatin on Lipopolysaccharide-induced Acute Lung Injury in Rats based on TLR4/MyD88/NF-kappa B pathway[J]. HeBei Med, 2019, 25(8): 1299-1303.

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2019.08.018 OR http://www.hbyxzzs.cn/EN/Y2019/V25/I8/1299

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