ABSTRACT
Objective To investigate the protective effect of continuous intravenous infusion of Isoproterenol (ISO)on myocardial mitochondria of early septic rats and the corresponding mechanism.Methods Thirty Sprague Dawley (SD)rats were randomly divided into 5 groups (6 cases per group):control group,endotoxin group,ISO small-dose group,ISO medium-dose group and ISO large-dose group.Endotoxin group and ISO intervene group received same management apart from drug intervention:receiving intravenous injection of lipopolysaccharide (LPS)10 mg/kg followed by an continuous intravenous infusion of 9 g/L saline 1 mL/h or ISO 0.06 μg/(kg · min),0.30 μg/(kg · min)and 0.60 μg/(kg · min).Control group received intraperitoneal injection and continuous intravenous infusion with the same amount of 9 g/L saline.The primary endpoint of the study was 24 hours after injection of 9 g/L saline or LPS.Serum creatine kinase (CK) and creatine kinase isoenzyme (CK-MB),oxidative and nitrosative stress levels and swelling of isolated heart mitochondrion were detected.The pathological changes of the myocardium and morphologic changes of the heart mitochondria were observed through light microscope and scanning electron microscope,respectively.Results The levels of CK,CK-MB,nitric oxide (NO) content,inducible nitric oxide synthase (iNOS) activity and malondialdehyde (MDA)content in endotoxin group were increased compared with control group (all P ＜ 0.05),while the superoxide dismutase (SOD) activity decreased [(11.543 ± 1.080) U/mg prot vs (9.892 ±0.815) U/mg prot,P ＜0.05].The morphology of the heart mitochondria significantly changed (such as swelling,disordered arrangement,crest fracture,fusion and cavitations,and so on).ISO intervention significantly decreased the levels of CK,CK-MB and mitochondrial swelling (all P ＜ 0.05) and increased the SOD activity (all P ＜ 0.05).The levels of NO content,iNOS activity and MDA content were significantly decreased in small-dose group [(10.823 ± 2.240) μmol/g prot vs (7.917 ± 2.203) μmol/g prot,(0.045 ± 0.008) U/mg prot vs (0.033 ± 0.003) U/mg prot,(1.663 ± 0.618) mmol/mg prot vs (0.768 ± 0.312) mmol/mg prot,all P ＜ 0.05],while the levels of iNOS activity and MDA content were significantly increased in medium-and large-dose group (all P ＜ 0.05) ; compared with medium-dose group,the degree of mitochondrial swelling in large-dose group increased (1.160 ± 0.186 vs 1.393 ± 0.128,P ＜ 0.05).The pathological changes of the myocardium mitochondria significantly improved.Conclusions The myocardium and myocardial mitochondria of early septic rats were damaged,continuous intravenous infusion of low-dose ISO revealed protective effect on these damages,and the corresponding mechanism may relate to the decrease of the oxidative and nitrosative stress.
ABSTRACT
Objective To investigate the effect of concurrent exercise intervention in metabolic endotoxemia induced by high-fat diet in rats,and further understand the damage of liver mitochondrial ultramicrostructure.Methods Eighteen SD rats with the weight of 100g were randomly divided into 3 groups:group A (standard diet group),group B(high-fat diet group) and group C (treadmill-trained group with high-fat diet).Training (1 hour/d) initiated at the same time as the HF diet was fed.After being raised for 6 weeks,the rats was euthanized and weighed up.Blood samples were taken and the levels of serum lipid were detected.The levels of serum endotoxin were detected by enzyme-linked immunoadsorbent assay.The membrane potentials of isolated mitochondrion were detected by flow cytometry instrument and the morphologic changes in mitochondria in liver were observed by electronic microscopy.Results In group B,the levels of endotoxin increased significantly(2.916 ± 0.761 rs 5.454 ± 1.254,t =-4.236,P ＜ 0.05),and the liver mitochondrial density and membrane potential also increased significantly compared with group A after 6 weeks (4.330 ±0.501 vs 3.507 ±0.532,t =2.759,P ＜0.05;l.660 ±0.202 vs 0.473 ±0.064,t =13.712,P ＜0.05).But there was no markedly different in serum endotoxin between group B and group C (4.972 ± 1.757 vs 5.454 ± 1.254,t =-0.547,P ＞ 0.05).Compared with group B,the liver mitochondrial density of group C decreased significantly (4.330±0.501 vs 3.581 ±0.188,t =3.426,P ＜ 0.05).The mitochondrial ultrastructurctural changes in each group were not obvious.Conclusions The rats fed with high-fat diet for 6 weeks can reach the state of metabolic endotoxemia.The increasing levels of the liver mitochondrial membrane potential caused by metabolic endotoxin may affect the happening and development of other diseases in the future.Concurrent exercise can not decrease the level of endotoxin.It also shows that metabolic disease caused by high-fat diet should be prevented by moderation in eating and drinking.