High intensity interval exercise reduced necroptosis and inflammation response of hippocampal neurons in type 2 diabetic mice
Objective:To investigate the effect of high-intensity interval exercise(HIIT)on necroptosis and neuroinflam-mation in hippocampus of type 2 diabetes mellitus(T2DM)mice.Method:Male C57BL/6 mice fed with high-fat for ten weeks and then injected with streptozotocin(STZ)to establish the model of T2DM mice.Mice were divided into normal control group(CON,n=10),T2DM mod-el group(T2DM,n=10),and T2DM exercise group(HIIT,n=10).Mice in HIIT group received treadmill training for 7 weeks.At the end of the experiment,the necroptosis of hippocampal neurons was determined by lactate dehydrogenase(LDH)content and propidium iodide(PI)staining.The NOD-like receptor protein 3(NLRP3)level was examined by immunofluorescence staining.The mRNA expressions of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in hippocampus were evaluate by quantitative real-time polymerase chain reaction(qRT-PCR).The level of necroptosis and inflammatory cytokines related proteins in hippocam-pus were measured by the Western Blot.Result:Compared with the CON group,the LDH release level was significantly increased(P<0.0001),the number of PI-stained positive cells and the expression level of necroptosis related proteins were increased in T2DM group.The fluorescence intensity of NLRP3,the expression of NLRP3,caspase-1,cleaved caspase-1 protein and inflammatory cytokines iNOS,IL-6,TNF-α and IL-1β were significantly increased(P<0.05)in T2DM group.After 7 weeks of the HIIT intervention,the hippocampal LDH release level of HIIT group was significantly lower than T2DM group(P<0.0001),the number of PI-stained positive cells and the expressions level of necroptosis related proteins was also decreased.The fluorescence intensity of NLRP3 and the expres-sion of NLRP3,caspase-1,Cleaved caspase-1 protein and the expression levels of proinflammatory factor were all decreased in HIIT group compared to the T2DM group(P<0.05).Conclusion:Necroptosis was found in the hippocampal tissue of T2DM mice.HIIT can inhibit the necroptosis and eventually reduce the inflammatory response in the hippocampal tissue of T2DM mice.
type 2 diabetes mellitusnecroptosisneuroinflammationhigh intensity interval exercise