Study On Mice Model Of Paraquat-Induced Acute Lung Injury And The Role Of Complement In Its Pathogenesis

Objective: To establish mice model of acute lung injury induced by paraquat and investigate the role of complement system in pathogenesis of the acute lung injury.Methods: (1) The control mice treated with saline intraperitoneally. The PQ groups got the intraperitoneal injection of paraquat with different dose(10mg/kg, 20mg/kg 50/mg/kg body weight). The mice were sacrificed at 48h after administration, BALF was collected to analyze total protein by the method of Bradford, and lung tissues were processed for either measurement of MPO activity or histopathologic analysis. (2) The mice treated with a single dose of PQ(20mg/kg body weight)and were killed at Oh and 4h 12h 24h, 48h after administration. Blood samples were collected for measurement of serum C3c by turbidity immuneassay. The expressions of C3 C5a and C1q in lung tissues were examined by immunohistochemistry. Total protein in BALF, MPO activity and histopathologic analysis of lung tissue were processed as mentioned above. (3) The PQ groups (P10 P20)got the intraperitoneal injection of paraquat with different dose (10mg/kg and 20mg/kg body weight) . The mice that received CVF (C10 C20)were given three intraperitoneal injections of 2.5μg of CVF at 48h 36h and 24h prior to PQ intoxication. The mice were sacrificed at 48h after administration, BALF was collected to analyze total protein and lung tissues were assayed for MPO activity. (4) A separate experiment was performed that a total of 40 mice were divided into four groups. The mice were treated with the same way as above only for observation the survival rates.Results: (1) Pathological damage of lung was in positive correlation with the dose and time course of PQ administration, accompanied with the activity of MPO PMN infiltration and the concentration of TP in BALF increasingly. (2) The serum C3c level elevated at 12h after PQ intoxication (20mg/kg body weight), reached the peak at 24h and continued up to 48h. At the same time we found C3 deposition mainly at the lung vascular endothelial, interstitium and bronchiole epithelium at 4h after intoxication ,but the staining weakened from 12h. In addition, we could observe the expression of C1q and C5a in vascular endothelial at 4h and then staining deepen gradually. (3) It was shown that the pathological damage was attenuated by pretreatment of CVF and fewer inflammatory cells infiltrated. The 5d survival rate is 20% in the P10 group, while all the mice of C10 group survived. The 3d survival rate of the P20 group improved from 0% to 70%with CYF administration. Conclusions: (1) We successfully established mice model of acute lung injury induced by paraquat. (2) The research suggested that the acute lung injury is in a time- and dose-dependent manner. (3) The complement is activated during early stage of acute lung injury induced by paraquat. The complement may play an important role in the pathogenisis of paraquat -induced acute lung injury.