Effect of resveratrol on myocardial energy metabolism in sepsis rats / 中华危重病急救医学

ABSTRACT

Objective To investigate the influence of resveratrol (RES) on myocardial energy metabolism in sepsis rats and its mechanism.Methods Twenty Sprague-Dawley (SD) rats were divided into four groups according to the random number table,5 rats in each group.The sepsis model was reproduced by intraperitoneal injection of lipopolysaccharide (LPS) 10 mg/kg,and the rats in sham group were injected intraperitoneally with the same amount of saline.The rats in RES treatment group (RES group) were injected RES 8 mg/kg 10 minutes before LPS injection,and those in RES combined with the silent information regulator 1 (sirt1) inhibitor group (RES + sirtinol group) were injected sirtinol 1 mg/kg followed by RES 8 mg/kg 10 minutes before LPS injection.The rats were sacrificed 6 hours later,and the heart was harvested.The myocardial ultrastructure was observed by transmission electron microscope.The expression of sirt1 protein was detected by Western Blot.The cytochrome C oxidase (CCO) activity was determined by ultraviolet spectrophotometry.The content of adenosine triphosphate (ATP),adenosine diphosphate (ADP),and adenosine monophosphate (AMP) were detected by high-performance liquid chromatography (HPLC).Results Under transmission electron microscopy,the mitochrondria in myocardium in sham group was normal,and mitochrondria was swollen and derangement in LPS group and RES + sirtinol group,but it was not significant in RES group.Compared with sham group,the sirt1 protein expression in LPS group was decreased (gray value0.602 ± 0.038 vs.0.902 ± 0.037,P ＜ 0.05),the CCO activity was declined (U/mg0.344 ± 0.019 vs.0.600 ± 0.023,P ＜ 0.05),the contents of ATP,ADP,and AMP were decreased [ATP (μg/g)89.958 ± 7.570 vs.157.460 ± 6.737,ADP (μg/g)164.658±6.742 vs.251.608±5.191,AMP (μg/g)179.926±7.303 vs.276.262±5.546,all P ＜ 0.05].Compared with LPS group,the sirt1 protein expression in RES group was increased (gray value0.874±0.017 vs.0.602±0.038,P ＜ 0.05),the CCO activity was increased (U/mg0.574±0.013 vs.0.344±0.019,P ＜ 0.05),the contents of ATP,ADP,and AMP were increased [ATP (μg/g)147.686± 8.853 vs.89.958 ± 7.570,ADP (μg/g)245.860±7.111 vs.164.658±6.742,AMP (μg/g271.260±6.658 vs.179.926±7.303,all P ＜ 0.05].Compared with RES group,the sirt1 protein expression in RES + sirtinol group was decreased (gray value0.636±0.030vs.0.874±0.017,P ＜ 0.05),the CCO activity was declined (U/mg0.369 ± 0.040 vs.0.574 ±0.013,P ＜ 0.05),the contents of ATP,ADP,and AMP were decreased [ATP (μg/g)97.942± 11.257 vs.147.686 ± 8.853,ADP (μg/g)168.888±8.965 vs.245.860±7.111,AMP (μg/g)175.498±6.993 vs.271.260±6.658,all P ＜ 0.05].Conclusion RES could improve myocardial energy metabolism in sepsis rats,in which sirt1 is an important factor.