Atorvastatin Calcium Could Alleviate The Pulmonary Fibrosis Induced By Paraquat Poisoning

Objective: Observe the effects of atorvastatin calcium on pulmonary fibrosis made by paraquat and explore the potential mechanism.Methods: Total of 120 healthy adult SD(Sprague-Daley,SD) rats were randomly divided in 7 groups: normal saline group(NS), paraquat poisoned group(PQ), paraquat received atorvastatin calcium(STN) at the dose of 10/20/40mg/kg.day(STN1/2/3), paraquat received both atorvastatin calcium at the dose of 40mg/kg.day and pioglitazone group(PGT group), and paraquat received both atorvastatin calcium at the dose of 40mg/kg.day and GW9662 group(GW9662 group). We made the rat model of paraquat(PQ)-induced pulmonary fibrosis by the way of intraperitoneal injection paraquat at the mount of 20mg/kg. And we used normal saline to make the group normal saline in the same way. We made STN1/2/3 in the way of intraperitoneal injection paraquat at the mount of 20mg/kg and intragastric administration STN at the mount of 40mg/kg.day.Weadded PGT at the dose of 10mg/kg.day and GW9662 at the dose of 1 mg/kg.day on the paraquat- atorvastatin calcium model(40 mg/kg.day). All the SD rats were sacrificed at day 14. And we compared the pathology of lung tissue, the number of various inflammatory cells in lavage fluids of rats, the amount of hydroxyproline and the amount of protein and the level of m RNA of TGF-β1 of lung tissues in serums among groups.Results: Sacrificed all mouse interrupted by drugs and stained by HE(Hematoxylin-eosin,HE), we could see that the exudation of inflammatory cell in alveoli and interstitial lung and formation of fibrosis in lung tissue of paraquat poisoning, and localized fibrous lesions hyperplasia obvious. After intervention by atorvastatin calcium, inflammatory cells in alveolar and lung tissue else decreased and pulmonary interstitial fibrosis alleviated varying degrees of ease in the experimental STN2 and STN3 groups. Contrast to paraquat poisoning group, pathology scores of STN2 group and STN3 group were significantly decreased. Contrast to STN3 group, exudation of inflammatory cells in lung tissue decreased and increased, respectively, after intervention by GW9662 which was the inhibitor of PPARγ and PGT which was the activator of PPARγ, while the level of pulmonary fibrosis increasing significantly and reducing visibility respectively.The pathological scores also increased and decreased respectively. The number of various inflammatory cells in lavage fluids of rats, the amount of hydroxyproline, the amount of protein and m RNA of TGF-β1 in lung tissues in PQ poisoned group,were more than NS Group. And indicators in both STN2 and STN3 groups were less than PQ group. The number of various inflammatory cells in lavage fluids of rats and the amount of hydroxyproline, the amount of protein and m RNA of TGF-β1 in lung tissues in PGT group were less than STN3 group and the same indicators in GW9662 group were more than STN3 group.Conclusion: Atorvastatin calcium could alleviate the paraquat(PQ)-induced pulmonary fibrosis. And this protection was in a dose-dependent manner. The mechanism may be achieved by the action to PPARγ.