The protective effect of p38MAPK inhibitor on the paraquat-induced acute lung injury in rats / 医学研究生学报

ABSTRACT

Objective Though paraquat (PQ) is highly toxic, there is still no effective treatment for PQ poisoning .The aim of the article was to study the protective effect and mechanism of the p 38 mitogen-activated protein kinase ( MAPK) inhibitor SB203580 on PQ-induced acute lung injury in rats . Methods 72 SD rats were randomly divided into three groups ( n=24 ) normal saline (NS) group, PQ poisoning group and p38 inhibitor SB203580 intervention (PQ+SB) group.The arterial blood gas analysis, lung wet and dry ratio (W/D),the expression of tumor necrosis factor-α(TNF-α), the superoxide dismutase (SOD) level and the pathological changes of lung tissues were recorded at different time points after drug intervention . Results On the 1st , 3rd, 5th days after drug intervention in PQ group, the alveolo-arterial oxygen partial pressure difference (PA-aO2) [(45.67 ±4.17), (68.78 ±6.63), (80.23 ±7.12 ) mmHg ], the lung tissue TNF-αexpression (14.63 ±3.10], [18.24 ±2.98], [16.22 ±2.79] pg/mg) and W/D ([4.931 ±0.034], [5.020 ±0.064], [5.079 ±0.016]) in-creased gradually to a peak on the 3rd day, while the SOD level de-creased respectively on the 1st , 3rd, 5th days after drug intervention ([175.26 ±7.98], [167.57 ±8.05], [160.24 ±6.78] U/ug) (P<0.05).Compared with PQ group, PQ+SB group got a decrease in the PA-aO2([80.23 ±7.12] vs [44.17 ±4.16]), the lung tissue TNF-αexpression ([16.22 ±2.79] vs [9.48 ±2.72]) and W/D ([4.805 ±0.070] vs [5.079 ±0.016]) (P<0.05), while the pulmonary SOD level increased in comparison with PQ group ([125.89 ±6.65] vs [160.24 ±6.78]) (P<0.05). Conclusion The p38MAPK inhibitor SB203580 plays a certain protective role in PQ-induced acute lung injury by reducing inflammation and improving antioxidant capacity .