An evaluation of effects on induction of acute lung injury in mice by different doses of lipopolysaccharide and different durations / 中国中西医结合急救杂志

ABSTRACT

Objective To observe the changes of inflammatory factors in acute lung injury (ALI) in mice induced by lipopolysaccharide (LPS), and to explore the influence of different doses of LPS on ALI onset and progress at different time points. Methods Intratracheally, LPS at the dosages of 2.5, 5.0, 7.5 and 10.0 mg/kg were administered to a total of 210 C57BL/6 mice, and according to the difference in dosage, they were divided into four groups. The ALI model was replicated by intratracheally dropping of LPS. And a normal control group and a normal saline control group were established (each, n=10). The changes of index of pathological lung tissue and lung tissue wet/dry (W/D) ratio were observed at 1, 2, 4, and 8 hours after injury, and simultaneously, the levels of norepinephrine (NE), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and protein in serum and bronchoalveolar lavage fluid (BALF) were detected. Results ①The degree of lung injury induced by LPS was dose-and time-dependent.②With the increase of LPS dosage and prolongation of time, in LPS group, the lung W/D ratio and the index of pathological lung tissue were increased;additionally, the levels of NE, TNF-α, IL-6 and protein in serum or BALF were also significantly increased. The critical occurrence point of acute respiratory distress syndrome (ARDS) with specific characteristics was at 5.0 mg/kg of LPS acting for 4 hours [lung W/D ratio 4.97±0.41, index of pathological changes of lung tissue (score) 5.60±1.52; serum NE (ng/L) 379.99±27.65, TNF-α (ng/L) 159.15±20.62, IL-6 (ng/L) 177.15±29.13;BALF NE (mg/kg)105.85±13.66, TNF-α(mg/kg)227.22±48.01, IL-6 (mg/kg)251.55±54.08, total protein (g/L)1.59±0.37]. The injury induced by LPS acting for 8 hours in the dosage group 10.0 mg/kg was the most significant in comparisons with other groups of dosages at the same time points [lung W/D ratio5.10±0.18 vs. 5.01±0.43, 5.01±0.19, 4.91±0.30; index of pathological changes of lung tissue (score) 9.20±1.48 vs. 8.00±1.00, 6.00±1.22, 4.40±0.89;serum NE (ng/L) 447.43±34.63 vs. 419.23±30.62, 391.16±54.91, 372.59±51.52; TNF-α(ng/L) 205.99±31.31 vs. 181.01±25.11, 161.01±13.98, 138.83±28.95; IL-6 (ng/L) 233.76±34.84 vs. 206.21±26.68, 186.58±26.54, 156.99±28.83;BALF NE (mg/kg)190.82±41.75 vs. 153.30±35.42, 122.64±25.15, 80.23±13.69;TNF-α(mg/kg)305.24±72.99 vs. 292.77±38.07, 249.60±35.20, 193.63±10.83; IL-6 (mg/kg) 354.81±67.79 vs. 303.02±54.24, 272.43±32.34, 197.64±12.35;total protein (g/L)2.31±0.30 vs. 2.02±0.26, 1.62±0.19, 1.10±0.24, P<0.05 or P<0.01]. Conclusions The severity of ALI induced by LPS in mice was positively correlated to LPS dosage and duration of its action. After administration of LPS 5 mg/kg for 4 hours, remarkable characteristic manifestations of ARDS occur in mice, reaching the critical point.