| Objective: As one of the most common clinical emergency poisoning, Paraquat(PQ) intoxication have a very high mortality, whose major cause of death is respiratory failure. The precise mechanism of pulmonary toxicity remains uncertain and there is no effective treatment for PQ poisoning . The present study was to explore the effect of oxidative stress, nuclear factor kappaB(NF-κB) and tumor necrosis factor alpha(TNF() in paraquat-induced lung injurys, also the curative effect of antioxidative sedatives propofol for PQ poisoning . Methods: Eighty-eight male Wistar rats were divided in 3 groups.1 Propofol group (n=40), which received PQ(50mg/Kg body weight) diluted with 1ml saline intragastrically and propofol at a dose of 10mg/Kg (1ml/Kg) 1 hour after PQ, twice daily,intraperitoneally. 2 Intoxication group(n=40),which was treated identically to the propofol group except for the substitution of 0.9% saline for propofol. 3 Control group (n=8),which received 1ml of saline, intragastrically. Rats in propofol group and intoxication group were killed 24 hours, 3, 7, 14 and 28 days after paraquat treatment by withdrawal from heart , bronchoalveolar lavageκBAL) and lung tissue specimens was carried out. Rats in control group received the same treatment. Blood samples, bronchoalveolar lavage fluid κBALF) and lung homogenate specimens were detected for baseline oxidative activity measurements: malondialdehyde (MDA) and superoxide dismutase(SOD). Cell count of BALF and hydroxyproline (HPY) levels in homogenate were also measured. Pathology of lung tissue were oberserved by hematoxylin-eosion(HE) staining and Masson staining. The expression of NF-kB p65 and TNF( in lung tissue were detected by immunohistochemistry (IH) staining. Result: 1 Intoxication manifestations (1)Intoxication group: Intoxication manifestations occurred in rats only 0.5~2 hours after PQ and was most serious during the first three days. Respiratory manifestations system such as tachypnoea were obvious. Manifestations of mind-nervous or digestive system and a descent of body weight were also seen commonly . Intoxication manifestations were relieved gradually after the first 3 days and the body weight increased on the 7th day. (2) Propofol group: While intoxication amelioration was observed in propofol group,there was no significant increasement of body weight compared with intoxication group. 2 Serum, BALF and homogenate measurement We observed significantly larger levels of MDA in serum,BALF and homogenate in intoxication group,especially at 24h and the 3th day, and propofol suppressed MDA levels significantly. No significant changes were found for SOD concentration in serum and homogenate between any two groups in our study. Cell counting of BALF in intoxication group increased significantly at all intervals except for the 28th day and propofol decreased the cell amount significantly at 24h, the 3th and the 7th day. An increace for HPY measurements in homogenate was seen seven days after PQ significantly in the intoxicated rats and there were no significant changes of HPY measurements in propofol group compare with intoxication group at the same time point. 3 HE staining The normal alveolar wall was thin and clear and there was no infiltration of inflammatory cells. Pulmonary edema, haemorrhage or extrusion of macrophages and neutrophils were seen in intoxication group, especially during the first 3 days and propofol relieved the acute lung lesions. We observed proliferation of collagen fibers and fibrous thickening of the alveolar wall 14 days after PQ intoxication. Propofol didn't relieve the lung fibrosis in our study. 4 Masson staining In control group there were a small quantity of collagen fibers stained green or blue on the bronchus dissepiment and the septal surface. As the same as HE staining, proliferation of the stained collagen fibers and thickness of the alveolar wall were seen in intoxication rats and no significant amelioration of fibrosis were found in propofol treatment. 5...
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