Effects Of Atorvastatin On The Lung Injury Induced By Acute Paraquat Poisoning

PART I:Protective effect of atorvastatin on lung injury induced by acute paraquat poisoningObjective:To Study the protective effect of atorvastatin on the lung injury induced by acute paraquat poisoning in rats.Methods:Forty healthy SD rats were randomly divided into four groups.Normal control group, paraquat poisoning model group, atorvastatin treatment of low and high dose group.Each group has ten animals. Paraquat poisoning model group and the treatment groups were given paraquat80mg/kg gavage; The treatment group was given atorvastatin20mg/kg,40mg/kg gavage for7days respectively.The control group and the paraquat poisoning group were given the same volume of normal saline. The animals were anesthetized with10%chloral hydrate24hours after the last gavage. Take the right lower lung tissue fixed with4%formaldehyde and do paraffin cuts. Observe the pathological changes of HE staining of lung tissue. Take the right upper lung to detect the level of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX). Statistical Analysis:The quantitative data of continuous variables were expressed as mean±S.E.M. Statistical significance was tested by one way analysis of variance (ANOVA). P<0.05was considered statistically significant.Results:The pathological changes in lung tissue after HE staining:compared with the control group, paraquat poisoning lung injury is obviously serious. Treatment groups reduce the lung injury. The high-dose group’s lesions are the lightest and the low-dose group is the heaviest. SOD、GSH-PX determination results:compared with the control group, the paraquat poisoning group significantly reduced (paraquat poisoning group SOD (U/mgprot)29.74±2.91, GSH-PX(vitality units)5.09±1.04; control group SOD(U/mgprot)92.46±3.87, GSH-PX (vitality units)27.83±1.85)(P<0.05); The treatment group showed significantly higher level(P<0.05); Compared between the treatment groups, the high dose group is higher (SOD(U/mgprot))(SOD (U/mgprot)57.96±1.40,GSH-PX (vitality units)13.46±2.07), the low dose group (SOD(U/mgprot)39.92±2.03,GSH-PX (vitality units)8.26±1.18))(P<0.05).Conclusion:Atorvastatin has protective effect on rat acute paraquat poisoning, and can increase SOD, GSH-PX activity. PART Ⅱ The role of Rho/ROCK signaling pathway in acute paraquat poisoning lung injury and the intervention effect of atorvastatin.Objective:To Study the role of Rho/ROCK signaling pathway in acute paraquat poisoning lung injury and the intervention effect of atorvastatin. Methods:To Choose40healthy adult SD rats. Randomly divided into normal control group, paraquat poisoning group, atorvastatin treatment of low and high dose group, each group has ten animals. Paraquat poisoning group and the treatment groups were given paraquat80mg/kg gavage; The treatment groups were given atorvastatin20mg/kg,40mg/kg gavage half an hour after giving paraquat, which was repeated at the same time for7days; the control and poisoning group were given the same volume of normal saline. The animals were anesthetized with10%chloral hydrate24hours after the last treatment. Incision along the sternum midline, exposure the pleural.Take the right lower lung tissue fixed with4%formaldehyde and do paraffin cuts. Do the immunohistochemistry to detect Rho and ROCK expression; Take the left lung tissue to do the reverse transcription-polymerase chain reaction(RT-PCR) detection of Rho A, ROCK m RNA transcript levels.Results:In the control group, both transcription and expression level of Rho A and ROCK were less.Compared with the control group, transcriptional levels and immunohistochemical results of Rho A, ROCK in lung tissue significantly increased (P<0.05). When atorvastatin intervention was given, transcription and expression level of Rho A and ROCK decreased compared to the poisoning group(P<0.05).Conclusion:Rho/ROCK signaling pathways may be associated lung injury and fibrosis induced by acute paraquat poisoning. Atorvastatin has protective effect on the lung injury, the mechanism maybe inhibit Rho/ROCK kinase pathway.