Study On Pathological Injury And Apoptosis Of Heart In Obese Mice Induced By Intranasal Infusion Of Escherichia Coli

Heart and lung have close relationship in structure and function,and adverse cardiac events are associated with bacterial pneumonia.Obesity has been linked with various cardiovascular diseases and increased susceptibility to bacterial infection.However,obesity paradox researchers believe that obesity has many adverse effects,but it is beneficial to the survival of pneumonia patients and improve the prognosis.In the state of non-lethal Escherichia coli infection,the injury of lung and the change of T lymphocyte subsets in peripheral blood as well as the disorder of lipid metabolism in obese mice were less serious than the normal mice.At present,the cardiac dysfunction caused by pulmonary infection has attracted the attention of many researchers,but the study of obese mice on the pathological injury and apoptosis of heart tissue of E.coli infection has not yet been reported.Male ICR mice were selected for intranasal instillation of PBS or E.coli with 8-week normal/high-fat diet-induced normal and obese(DIO)mice and divided into 4 groups: Normal-PBS,Normal-E.coli,DIO-PBS,DIO-E.coli.The body weight,serum TG,TC content and changes of cardiac histomorphology,inflammation and oxidative stress status,as well as apoptosis rate and representative markers of protein and mRNA expression levels in the mitochondrial dependent apoptosis pathway were detected at 0h(pre-infection),12 h,24h,and 72 h post-infection by H.E staining,Masson staining,ELISA,biochemical method,flow cytometry,Western blotting and Quantitative real-time PCR.Physical signs and tissue injury results showed that the body weight,heart weight,Lee’s index and total TG,TC content in serum in the DIO-PBS/-E.coli group were significantly higher than those in the Normal-PBS/-E.coli group(p<0.01).And,organ index in the DIO-PBS/-E.coli group was increased,but had no significance(p>0.05).Meanwhile,the cardiac organ index of Normal-/DIO-E.coli group was significantly higher than that of Normal-/DIO-PBS group(p<0.05),while the cardiac weight was increased,but had no significance(p>0.05).Macroscopic and microscopic observations showed that both the volume and the left ventricular heart cavity of the DIO-PBS/-E.coli group were increased,and the myocardial space was slightly widened,while there was no significant macroscopic changes after E.coli infection,but local vacuolar degeneration and cytoplasmic dissolution in myocardial cells were observed.Inflammtory levels results showed that the contents of IL-6,IL-8,Leptin and Resistin in DIO-PBS/-E.coli group were significantly higher than those in Normal-PBS/-E.coli group(p<0.05).And,the contents of IL-1β,IL-6,IL-8,TNF-α,Leptin and Resistin were significantly risen from 12 h to 24 h after E.coli infection.Oxidative stress status results showed that compared with the Normal-/DIO-PBS groups,the activity of GSH-Px and the content of GSH in the heart of the DIO-PBS group increased significantly(P<0.05).And,the activity of CAT,SOD and the content of MDA increased,which showed no significant difference(P>0.05).Meanwhile,the above mentioned oxidation markers of Normal-/DIO-E.coli group were significantly increased(p<0 05)at 12 h or 24 h after E.coli infection.Cardiomyocyte apoptosis results showed that the cardiac apoptosis rate,and caspase-3,caspase-9 and bax mRNA as well as protein,along with bax/bcl-2 ratio all significantly(p<0.01)increased in the DIO-PBS/-E.coli and Normal-E.coli groups contrasted with the Normal-PBS group,whereas bcl-2 mRNA and protein levels were significantly reduced(p<0.01).After E.coli infection,in comparison to the DIO-E.coli group,the above mentioned parameters except Leptin and GSH have a greater relative variation amplitude in the Normal-E.coli group,being the maximum at 12 h or 24 h,and approaching the initial status at 72 h.In conclusion,obesity induced by high-fat diet or E.coli infection both caused cardiac histomorphology damage,inflammatory reaction,oxidative stress and excessive cardiac apoptosis to some extent,of which cardiac apoptosis may be closely related to mitochondrial pathway.In addition,the changes of cardiac inflammation,oxidative stress and excessive apoptosis in DIO mice were smaller than those in Normal group after infected with E.coli,and the related mechanisms need to be further studied.