The Study Of Using Bosental Treal Acute Lung Injury Induced By Paraquat Poisoning In Rats

Background: Paraquat, the trade name for 1,1'-dimethyl-4,4'- bipyridinium dichlorideo It's function as weeding was found at 1960s. Paraquat inactivates quickly while contact with earth, no atmosphere pollution and residue exists. Since paraquat is excellent in weeding and also the poor price, it is widely used in ample agriculture country. The number of people who attempt to suicide or accidental poisoning is still high because the more chance to exposure. After intaked, liver, kidneys, heart, and neural organization would be damaged, and multiple organ function failure is induced. The major target organ is lung, acute lung injury and advanced pulmonary interstitial fibrosis is the most serious complication. The first two cases of paraquat poisoning were reported oversea in 1966, then all over the world had reported paraquat poisoning cases. In 1990s two paraquat poisoning cases were reported domestic. The mechanism is still indefinite and no special antidotes exist, so the mortality is high. Bosentan, a dual endothelin receptor antagonist, is widely used in treating pulmonary hypertension. It raises exercise tolerance, improves hemodynamics and also increases life quality. There is evidence that it play an important role in treating pulmonary interstitial fibrosis. Very few related literature was reported in bosentan therapy of paraquat.Objective:Our research study the therapy of bosentan in treating acute lung injury and pulmonary interstitial fibrosis induced by paraquat. Method:All 90 adult Wister male rats were randomly assigned to three groups, the paraquat poisoning group(rats were intragastric administration paraquat 50mg/kg body weight once at the beginning); the bosentan therapy group(rats were given bosentan 100mg/kg body weight intragastric administration half an hour after paraquat was given, then the same dose was given once a day); control group(rats were intragastric administration with physiological saline). At 3rd,7th,14th,21stday rats were sacrificed postanesthetic respectively after paraquat exposure, sample of lung tissue and venous blood were collected. Transforming growth factor-β1,endothelin-1,hydroxyproline in plasma and the lung homogenate were determined. Optical microscope and electronic microscope were performed to examine pathological changes in lung.Result: TGF-β1,ET-1,hydroxyproline of paraquat poisoning group were significantly higher than control group, the 21st therapy group was significantly lower than paraquat poisoning with the same days. Under optical and electronic microscope, the tissue damage of lung was aggravated, and reduced after bosentan was administrated.Conclusion:Bosentan can reduce inflammation factor releasing, and relieve lung injury. It has therapeutic effect on acute lung injury induced by paraquat poisoning.