Study On Effects Of Atorvastatin On NO And MDA In CLP Rat Model

Objective:Sepsis is a common inflammation syndrome induced by infection. Severe sepsis and sepsis shock are life threatening complications of infection and a major causes of death in intensive care units.Statins are widely recognized as hypolipemic drugs,but some studies have observed anti-inflammatory and immunomodulatory effects,known as pleiotropic.The purpose of this study is to investigate the change of nitric oxide and malon-dialdehyde in the sepsis rats and to investigate the interventional effects of atorvastatin.Method:Sepsis was replaced in rats by cecal ligation and puncture (CLP).A total of 75 male and famale Sprague-Dawley rats were randomly divided into three groups:sham-operation group, treated with starch (40mg·kg-1) and saline(2ml) for five days;CLP model group, treated with starch(40mg·kg-1) and saline(2ml) for five days,then were adopted to make the sepsis models of CLP; atorvastatin group, treated with atorvastatin (40mg·kg-1) and saline(2mL) for five days, then were adopted to make the sepsis models of CLP. Each group had 25 rats, and blood samples were collected at 0,2,6,10 and 24 hours after models were replaced. The levels of nitric oxide were measured. At the same time, hepatic tissue samples were collected and the contents of malondialdehyde were measured. ANOVA and LSD-test were used considering significant p<0.05.Result:The results showed that the levels of nitric oxide of plasma elevated in early period of 6 hours, and continued increasing, and got peak (329.04±21.15μmol·L-1)in 24 hours after models were replaced in CLP model group. In atorvastatin group the levels of nitric oxide of plasma showed an increase at 6 hours, but could be reduced in comparison with those of CLP model group, and got peak (209.53±10.68μmol·L-1) in 24h. In CLP model group the contents of malondialdehyde of hepatic tissue elevated in early period of 2 hours, then they did not change clearly from then on, but they incresed again and got peak (8.22±0.54 nmol·mgprot-1) in 24 hours after models were replaced.. In atorvastatin group, the contents of malondialdehyde of hepatic tissue were significantly decreased (6.32±0.35 nmol·mgprot-1) than those in CLP model group also.Conclusion:These results clearly demonstrate that atorvastatin is an effective agent that reduces the levels of nitric oxide of plasma and the contents of malondialdehyde of hepatic tissue in sepsis, independently of its well-known lipid-lowering effects. Thus, HMG-CoA (hydroxylmethyl glutaryl-coenzyme A) like atorvastatin have important anti-inflammatory effects on CLP model of rats.