| Objective:Reduced mitochondrial function is a major cause damage to the central nervoussystem and produces cognitive impairment. Research on improving the function ofneuronal mitochondrial damage under pathological conditions has importantsignificance. In this research，type2diabetic rats were induced by6weeks high-fat dietand low-dose streptozotocin-treated （STZ，30mg/kg），to study the eimprovement of12weeks of swimming training and EGCG separately or jointly intervention on on type2diabetic rats hippocampal mitochondrial dysfunction, studid theSIRT1/PGC-1pathway and downstream protein effects in it. discussed the effect andmechanism from Biosynthesis of mitochondria, oxidative stress resistance,mitochondrial fission and fusion, mitochondrial Autophagy to discuss its effect andmechanisms. The experimental results of present study support the neuroprotection ofexercise and EGCG,and also provide a new strategy of preventing and curingdiabetic encephalopathy.Methods:Type2diabetic rat model was successfully established,4weeks,8weeksand12weeks of rat hippocampus mitochondrial respiratory chain complexes Ⅰ, Ⅱ, Ⅲ,Ⅳ and Na+-K+-ATPase、Ca2+-ATPase activity was explored. The diabetic rats weredivided into diabetic control group,the diabetes exercise group,the diabetes druggroup,the diabetes exercise and drug jiotly group, For12weeks of exercise and EGCGseparately or jointly intervention. Western blot was used to detect the rat hippocampalSIRT1, PGC-1, NRF1, NRF2, TFAM, HO-1, NIX, BNIP3, PINK1and Parkin proteinexpression; RT-PCR was used to detect hippocampal mtDNA copy amount.The changesof rathippocampal mitochondrial respiratory chain complexes Ⅰ, Ⅱ, Ⅲ, Ⅳ and Na+ -K+atpase, Ca2+atpase activity were researched.Results:112weeks diabetic rats hippocampus mitochondrial respiratory chain enzyme Ⅰ、Ⅱ、Ⅲ、Ⅳ, Ca2+-ATPase activity and Na+-K+-ATP ase were showing a significantreduction in decline （P<0.01）;Exercise and EGCG medication, separately or jointlyintervention,could improve diabetes rats,hippocampus mitochondrial respiratorychain complex enzymes Ⅰ, Ⅱ, Ⅲ, Ⅳ and Na+-k+ATPase, Ca2+-ATPase activity indifferent level （P <0.05or P <0.01）.2Diabetes control group rats，hippocampal SIRT1, PGC-1, NRF1, TFAM andmtDNA, NRF2, HO-1were significantly lower than normal control group（P <0.01）;Exercise and EGCG medication separately or jointly intervention could improve theSIRT1, PGC-1, NRF1, TFAM, NRF2, HO-1protein expression and mtDNA copies indifferent level.3Diabetes control group rats hippocampal Mfn2, OPA1protein expression wassignificantly lower than normal control group （P <0.01）, and Drp1Fis1proteinexpression was significantly higher than that of normal control group （P <0.01）;Exercise and EGCG medication separately or jointly intervention could improve therat hippocampal Mfn2and OPA1protein expression in different level（P <0.05or P <0.01）, could reduce Drp1and Fis1protein expression in different level （P <0.05orP <0.01）.4Diabetes control group rats hippocampal NIX, BNIP3protein expressioncompared with were significantly lower （P <0.05）, Parkin significantly increasedcompared with normal control group （P <0.05）, PINK1protein expression comparedwith normal control group was no significant difference （P>0.05）; Exercise andEGCG medication separately or jointly intervention could improve the hippocampusNIX, different level BNIP3protein expression （P <0.05or P <0.01）, PINK1, Parkinprotein expression was no significant difference than diabetes control group（P>0.05）.512weeks of exercise and EGCG medication separately or jointly interventioncould improve Type2diabetes rat hippocampal mitochondria function. the jointlyintervention was ignificantly better than a single factor, indicating the jointly intervention have additive effects.Conclusions:112weeks of exercise training and EGCG medication separately or jointlyintervention can improve diabetes rat hippocampus mitochondrial respiratory chaincomplex enzymes activity，increase the ATP enzyme activity，improve the energymetabolism of mitochondria.2Exercise and EGCG medication separately or jointly intervention couldinhance type2diabetic rats hippocampal SIRT1/PGC-1pathway effect, improve theability of the biosynthesis of mitochondria and mitochondrial antioxidant capacity.312weeks of exercise and EGCG medication separately or jointly interventioncan improve the type2diabetic rats hippocampal Mfn2and OPA1protein expression，reduce Drp1and Fis1protein expression and improve diabetic rats hippocampalmitochondria imbalance of fusion and fission protein.412weeks of exercise training and EGCG medication separately or jointlyintervention could enhance the type2diabetic rats hippocampal NIX and BNIP3expression, improve rats,hippocampus mitochondrial autophagy ability，maintain thestability of the mitochondrial quality and quantity.5Exercise and EGCG medication jointly intervention may be an effectiveintervention strategies in mitochondrial dysfunction. SIRT1/PGC-1biologicalpathways could be an important target for regulation of mitochondrial function to thediabete，s prevention and treatment of the nervous system. |
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