| [Objective]To investigate the inflammatory factors and the effect of Sivelestat Sodium in rat model of acute paraquat poisoning.[Methods]128Wistar rats were randomly divided into4groups. Established the APQ rat model using the oral exposure way througing giving them high and low doses of Sivelestat Sodium intervention by intraperitoneal injection. Collected the serum and lung tissue after the rats were sacrificed and made the HE staining of lung tissue. For all experimental groups, we detected the expression levels of the tumor necrosis factor-a (TNF-a), interleukin-8(IL-8), neutrophil elastase (NE), transforming growth factor-β1(TGF-β1) in rat serum and lung tissue homogenates using the method of enzyme-linked immunosorbent assay (ELISA). Here we explored the antagonism of Sivelestat Sodium in lung inflammatory of the APQ rats.[Results]Part1. Research of inflammatory factors in rats of acute paraquat poisoning.1.1pathological changes of lung tissueThe structure of lung tissue in control group was normal and there was only slight inflammatory response. The visual observation of lung tissue in APQ rats appeared to be pale and has a more serious edema compared with the NS group. At the1th day, there was a small amount of macrophage infiltration in rats lung tissue. At the3th day, there was a growing number of inflammatory cells and macrophage infiltration and the inflammatory changes of the model group ws more obvious than the treatment group. At the7th day, it came a large number of inflammatory cells and neutrophil aggregation and a small number of fibroblasts began to appear. The interval between the alveolar was significantly wider with a large concentration of inflammatory cell infiltration which showed a typical diffuse alveolitis. At the21th day APQ group, a large number of fibroblasts appeared and the inflammatory cells were obviously reduced, but did not recover to normal levels compared with NS group.1.2The dynamic change of serum level of inflammatory factors in rats lung tissue(1) In each time point (except for the3th day), the expression levels in the model rats were significantly higher than the NS group, and the difference was statistically significant (P<0.05).(2) For each dose group, the expression levels of TNF-a, IL-8, NE, TGF-β1were seen significantly higher from1th to7th day. At the21th day, the index level began to decline. At all time points,there was a statistical difference of TNF-a, IL-8, NE between the APQ and NS groups.2Effects of Sivelestat Sodium in rat model of acute paraquat poisoning2.1pathological changes of lung tissueThe structure of lung tissue in control group was normal and there was only slight inflammatory response. At the1th day, the alveolar wall and alveolar septal capillary was infiltrated mildiy by neutrophil in the experimental group. The end side of the airway of the alveolar wall and the alveolar interval was infiltrated by a small amount of macrophage; At the7th day, part of the bronchial epithelial cells and alveolar epithelial cells were fell off and the alveolar septal was broadened and appeared edema. More neutrophils were appeared and the macrophages were aggregated in the alveolar cavity. The alveolar septal was thickened further and the alveolar structure was destructed, lymphocyte began to exude and the plasma cells were exudation increased. There were still a large number of macrophages proliferation and aggregation. At the21thday, alveolar cavity was mostly disappeared and alveolar was fracture. The number of cell nodule was increased, the main inflammatory cells were the lymphocyte and plasma cells, the fibroblasts can be saw occasionally. For the high and low dose group the inflammatory cells were few at the21th day than the7th day. However, compared with the control group, it still did not recover to the normal level.2.2The dynamic change of serum level of inflammatory factors in rats lung tissue(1) Compared to each dose group, the relevant factor expression in the model group were significantly higher than the high and low dose group with a statistically significant (P<0.05).(2) In the model group, the expression levels of TGF-betal factor increased slightly, but not significantly. The expression levels of TNF-a, IL-8, NE had a statistical difference between each time point.[Conclusions]1From the1th-21th days, lung histopathological showed a early inflammatory with the infiltration of macrophages and center myeloid gathered response. As the experiment progresses, the rats were significantly thickened alveolar septa, fibroblasts appears, the fibrous tissue hyperplasia. Inflammatory factors played an important roles in the inflammatory reaction.2The level of lung tissue and serum inflammatory cytokine in rats showed a change that first increased and then decreased and was consistent with the changes of lung tissue. So it could be considered to be the sensitive indicators of lung inflammation and fibrosis in APQ rats.3The level of inflammatory factor in the rats of Sivelestat Sodium was significantly lower than the model control group which was consistent with the pathology of lung tissue. It proved that Sivelestat Sodium played a certain antagonism of inflammatory lesions in the treatment of ALI induced by paraquat.4For experimental animals of Sivelestat sodium group, we did not detect a significant difference of TGF-β1with the control group, so we should make a further study about the antagonism of Sivelestat Sodium in pulmonary fibrosis of APQ rats. |
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