Effct Of Magnesium Sulfate On Lung Injury And Expression Of COX-2 In The Rat Model Of Paraquat Intoxication

【Backgroud and Objective】Paraquat intoxication can cause lung injurywith character of alveolar dropsy, pulmonary hemorrhage early. It candevelop to pulmonary interstitial fibrosis later. There is no specific antidotefor paraquat intoxication. COX-2 is known to be involved in pathologyprocess of inflammation and angiogenesis. It has an important role in asthma,lung injury, lung cancer and lung fibrosis. Magnesium sulfate as a calciumantagonist can dilate spasm of microvessel and arteriole caused by lunghypoxia, to improve hypoxia and respiratory function. In addition,magnesium sulfate could arrest the tendency and activation of eosinophilegranulocyte, increase stabilization of cell membrane, inhibit degranulation ofmast cell, and thus educe anti-inflammation effect. However, there is not anystudy about the effect of magnesium sulfate on the lung injury induced byparaquat intoxication.We aimed to investigate whether magnesium sulfatecould affect paraquat intoxication induced pulmonary injury of rats and itsprobable mechanism, to explore the pathology and development direction.【Method】Sixty male SD rats were assigned to three different groups:paraquat intoxication model group (PQ group); magnesium sulfate therapygroup (MS group); normal controlled group (NS group). PQ group was givenparaquat at a dose of 80mg/Kg by intragastric administration for once, andthen douched normal saline everyday. MS group was given paraquat at doseof 80mg/Kg by intragastric administration for once, and then douchedmagnesium sulfate (30 mg/Kg) everyday. NS group was given equivalentvolume of normal saline. Measurements were determined at 3rd, 7th, 14thand 21th days post exposure. Measured lung coefficient in order to knowabout the level of pulmonary edema, and observed the pathological changesof lungs in the microscope. Measured the expression of COX-2, CD-34 andcollagen fiber by immnohistochemistry and the level of Ca²⁺-ATP in lung homogenate.【Relults】①The lung structure of magnesium sulfate therapy group (MSgroup) has more integrated and lower injury compared with paraquatintoxication model group (PQ group). The lung coefficient of MS group wassignificant lower at the same time, and has significant difference between PQgroup and MS group (P＜0.05).â‘¡The expression of COX-2 was significantlyhigher in the rats for paraquat intoxication models (PQ group and MS group)compared with normal controlled group (NS group). The expression ofCOX-2 was significantly lower in the rats of MS group than PQ groupthroughout the research (P＜0.05).â‘¢The expression of MVD has nosignificant difference in the three groups at 3rd day (P-0.926). There hassignificant difference at 7th, 14th and 21th days in each other (P＜0.05). Therats of MS group have lower expression of MVD than PQ group.â‘£Theexpression of Ca²⁺-ATP was significantly decrease in the rats of PQ groupand MS group throughout the study. There is significant differencethroughout the study between PQ group and NS group (P=0.000). The levelof Ca²⁺-ATP of MS group was significant lower at 3rd, 7th, 14th day thanPQ group, (P＜0.05).⑤The intensity of collagen fiber has no significantdifference in the microscope for the three groups at 3rd day. The expressionof collagen fiber steady increase from 14th day, the microscope fields of PQgroup were full of collagen fiber, and appeared significant fibrosis. MS grouphas lower collagen fiber hyperplasia and structure destroy than PQ group.【Conclusion】These results suggest that the expression of COX-2 play animportant role in the pathogenesis of lung injury induced by paraquatintoxication. COX-2 participate the pathology process of alveolitis and lungfibrosis through participation inflammatory and angiogenesis. Magnesiumsulfate could lessen lung injury by reducing the expression of COX-2,decreasing angiogenesis and inhibiting calcium overload.