Protective Effects Of Atorvastatin Against Lung Injury In Septic Rats

Objective: As we all know that HMG-CoA reductase inhibitors (statins) are themost prescribed class of drugs in patients with cardiovascular disease now, and thereis evidence that statins have pleiotropic effects such as immunomodulatoryantioxidant properties. For the multiple beneficial effects, whether the inhibitionof sepsis-related inflammatory response became the focus. In this study, weestablished a septic rat model by the cecal ligation and puncture (CLP), then observedatorvastatin intervention of the rat pulmonary histopathologic changes, superoxidedismutase (SOD) activity, malondialdehyde (MDA) contents, and the impact ofthis model survival rate. Aimed to investigate the pulmonary protective effect of suchdrugs in sepsis.Methods: We used male Sprague-Dawley rats by cecal ligation and perforationsurgery to establish the model of sepsis. Six and eighteen hours after sepsis induction,each rat was treated by intraperitoneal injection of atorvastatin (0.2mg/kg bodyweight), and placebo group was treated by intraperitoneal injection of the NaCl0.9%as the same volume as above. Every groups were randomly dividedinto different subgroups. One group underwent closely observation after20hourssepsis induction, were manufactured for pulmonary histological specimens, and weremeasured SOD activity and MDA levels in lung. Then7days survival rate wasobserved in another group. Results: Compared to the placebo group the pathological changes of lung tissue of therats in the atorvastatin intervention significantly reduced. Survival rate was helicoptedfrom20%for placebo-treated rats to60%for atorvastatin-treated, and the survivaltime was extended from2.842±0.772days to5.418±0.698days. There arediscrepancies between the two groups (n=10, p=0.024). Assayed the pulmonary tissueof the rats, SOD activity in the intervention groups was significantly increased, andMDA levels were reduced. Examination among such groups had significant differents(n=10, p<0.01).Conclusions: Experimental data and the results demonstrate that atorvastatin canimprove the the rate of survival in rats with sepsis. As underlying mechanisms,atorvastatin could reduced the generation of superoxide radical in lung for alleviatingthe pulmonary injury. In addition statins may be considered as a sepsistreatment-assisted drug to assessment the effects and mechanism.