Effect of magnesium sulfate on lung injury and expression of COX-2 in the rat model of paraquat intoxication

Background and objective Paraquat intoxication can cause lung injury with character of alveolar dropsy, pulmonary hemorrhage early. It can develop to pulmonary interstitial fibrosis later. There is no specific antidote for paraquat intoxication. COX-2 is known to be involved in pathology process of inflammation and angiogenesis. It has an important role in asthma, lung injury, lung cancer and lung fibrosis. Magnesium sulfate as a calcium antagonist can dilate spasm of microvessel and arteriole caused by lung hypoxia, to improve hypoxia and respiratory function. In addition, magnesium sulfate could arrest the tendency and activation of eosinophile granulocyte, increase stabilization of cell membrane, inhibit deregulation of mast cell, and thus educe anti-inflammation effect. However, there is not any study about the effect of magnesium sulfate on the lung injury induced by paraquat intoxication. We aimed to investigate whether magnesium sulfate could affect paraquat intoxication induced pulmonary injury of rats and its probable mechanism, to explore the pathology and development direction. Methods Sixty male SD rats were assigned to three different groups: paraquat intoxication model group (PQ group); magnesium sulfate therapy group (MS group); normal controlled group (NS group). PQ group was given paraquat at a dose of 80 mg/kg by intragastric administration for once, and then douched normal saline everyday. MS group was given paraquat at dose of 80 mg/kg by intragastric administration for once, and then douched magnesium sulfate (30 mg/kg) everyday. NS group was given equivalent volume of normal saline. Measurements were determined at 3rd, 7th, 14th and 21st days post exposure. Measured lung coefficient in order to know about the level of pulmonary edema, and observed the pathological changes of lungs in the microscope. The expression of COX-2, CD-34 and collagen fiber by immnohistochemistry and the level of Ca2+-ATP in lung homogenate were measured. Results ①The lung structure of magnesium sulfate therapy group (MS group) has more integrated and lower injury compared with paraquat intoxication model group (PQ group). The lung coefficient of MS group was significant lower at the same time, and has significant difference between PQ group and MS group (P0.05). ②The expression of COX-2 was significantly higher in the rats for paraquat intoxication models (PQ group and MS group) compared with normal controlled group (NS group). The expression of COX-2 was significantly lower in the rats of MS group than PQ group throughout the research (P0.05). ③The expression of MVD has no significant difference in the three groups at 3rd day (P=0.926). There has significant difference at 7th, 14th and 21st days in each other (P0.05). The rats of MS group have lower expression of MVD than PQ group. ④The expression of Ca2+-ATP was significantly decrease in the rats of PQ group and MS group throughout the study. There is significant difference throughout the study between PQ group and NS group (P=0.000). The level of Ca2+-ATP of MS group was significant lower at 3rd, 7th, 14th day than PQ group, (P0.05). ⑤The intensity of collagen fiber has no significant difference in the microscope for the three groups at 3rd day. The expression of collagen fiber steady increase from 14th day, the microscope fields of PQ group were full of collagen fiber, and appeared significant fibrosis. MS group has lower collagen fiber hyperplasia and structure destroy than PQ group. Conclusions These results suggest that the expression of COX-2 play an important role in the pathogenesis of lung injury induced by paraquat intoxication. COX-2 participate the pathology process of alveolitis and lung fibrosis through participation inflammatory and angiogenesis. Magnesium sulfate could lessen lung injury by reducing the expression of COX-2, decreasing angiogenesis and inhibiting calcium overload.