| Background and Objective: Acute paraquat (PQ) intoxication can cause severe lung injury, which typically shows alveolar dropsy, pulmonary hemorrhage, and can develop to pulmonary interstitial fibrosis, leading to respiratory failure and death.There has no specific antidote for the routine treatment of paraquat intoxication. Matrix metalloproteinases (MMPs) are known to be involved in degradation of extracellular matrix, and maybe have an important role in the development of lung injury and pulmonary fibrosis. Losartan, a selective inhibitor of ATI receptors for angiotensin II (Angll), maybe inhibit the expression of MMPs, through which it could possibly prevent the development of myocardium injury, thickening of the myocardium, renal sclerosis. However, there has been almost no study of the effect of losartan on the lung injury induced by acute paraquat intoxication. We aimed to assess the role of MMPs(MMP-2 and MMP-9) in the genesis and evolution of lung injury induced by acute paraquat intoxication, andwhether losartan, a selective inhibitor of ATI receptors for angiotensin II (Angll), can reduce the expression of MMP-2, MMP-9 in lung injury induced by acute paraquat intoxication.Measurements: Fifty-four male SD rats were randomized to three groups: acute paraquat intoxication model group (group 1-P): the rats were given paraquat at the dose of 20mg/kg by intraperitoneal injection on day 0 for once, and then douched normal saline everyday. Losartan therapy group (group 2-L): the rats were given paraquat at the dose of 20mg/kg by intraperitoneal injection on day 0 for once, and then douched losartan (20mg/kg) everyday. Normal controlled group (group 3-N): the control rats were given equivalent volume of normal saline .Measurements were determined at 1st, 3rd, and 7th days post exposure. Lung coefficient was measured in order to know about the severity of pulmonary edema, and the level of hydroxyproline in the lung homogenate was measured. Microscopic examination of the pathological changes of lungs was carried out. The intensity of expression of MMP-2, MMP-9 was detected by immunohistochemistry.Main results: (D Progressive diffuse airsacculitis, with alveolar dropsy, pulmonary hemorrhage, hyaline membrane and inflammatory cell infiltration was found in PQ intoxicated rats. Losartan can slow down the development of the progressive diffuse airsacculitis. Compared with acute paraquat intoxication group (group 1), the level of lung coefficient oflosartan therapy group (group 2) were significantly lower at the 1st, 3rd, 7th day post exposure (PO.05). (g)The intensity of the expression of MMP-2 and -9, measured by immunohistochemistry, was significantly higher in the rats of acute paraquat intoxication model (both group 1 and group 2) compared with the control group (p <0.05) throughout the study. The intensity of the expression of MMP-2 was significantly lower in the rats of losartan therapy group (group 2) compared with acute paraquat intoxication group( group 1) at the 7th day post exposure, with significant difference(p<0.05), The intensity of MMP-9 expression was significantly lower in the rats of losartan therapy group(group 2) compared with acute paraquat intoxication group(group 1) at the 3rd, 7th day post exposure(p<0.05,p<0.01). ?Compared with acute paraquat intoxication group (group 1), the levels of hydroxyproline of losartan therapy group (group 2) were significant lower at the 3rd, 7th day post exposure (P<0.05).Conclusion: These results suggest that the expression of MMP-2 and MMP-9 plays an important role in the pathogenesis of lung injury induced by acute paraquat intoxication. Losartan could alleviate the lung injury from reducing the expression of MMP-2 and MMP-9.Losartan may have a role in preventing the pathological changes of pulmonary edema, pulmonary congestion and pulmonary hemorrhage, and the development of lung injury and pulmonary fibrosis induced by acute paraquat intoxication.
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