Chronic sleep restriction induces oxidative stress and inflammation in mice livers and brains

Abstract:

Objective：To investigate the effects of chronic sleep restriction（SR） on the function of livers and brains in mice，and to ex－plore the possible mechanism. Methods：Twenty C57BL/6J female mice at the age of 4 weeks were randomly divided into normal con－trol group（n=10） and SR group（n=10）. Then forty-five days after SR，the mice were observed for the changes of body weight，and the percentage of weight gain was detected in each group. Learning and memorizing abilities were measured by Morris Water Maze test. Liver，spleen and kidney wet weight index were detected in each group. The levels of tumor necrosis factor-α（TNF-α），inter－leukin-6（IL-6） and interleukin-1β（IL-1β） in the serum were detected by ELISA. The activities of superoxide dismutase（SOD） and contents of reduced glutathione（GSH） were measured by microplate assay. The protein levels of TNF-α，P53，Bcl-2-associated X protein（BAX） and B-cell lymphoma-2（BCL-2） were measured by Western blot. The expression of Ki-67 was analyzed by immuno－histochemical technique. Results：Compared with the normal control group，the mice in SR had a relatively slow body weight gain，a reduced spatial learning and memorizing capacities，an increased liver and kidney wet weight index（t=4.274，P=0.000；t=3.629，P=0.002），and a decreased spleen wet weight index（t=2.380，P=0.029）. The levels of TNF-α，IL-6 and IL-1β were higher in SR group [（53.719±4.128），（31.766±4.535），（41.916±4.819）] than those in the normal control group[（24.440±4.468），（14.265±3.718），（20.383±3.230）]（t=10.762，P=0.000；t=6.673，P=0.000；t=8.229，P=0.000）；the activities of SOD and contents of GSH in hippocampus and livers in SR group lowered significantly，compared with those in the normal control group（t=4.171，P=0.003；t=8.851，P=0.000；t=7.138，P=0.000；t=5.390，P=0.000）. Compared with that of normal control group，the expression level of TNF-α[（0.702±0.088），（0.818±0.074）]，P53[（0.626±0.103），（1.225±0.116）] and BAX[（0.978±0.078），（1.120±0.135）] in hippocampus and livers in－creased significantly（t=13.688，P=0.000；t=11.682，P=0.000；t=6.991，P=0.000；t=10.023，P=0.000；t=13.721，P=0.000；t=10.422，P=0.000），while the expression level of BCL-2[（0.365±0.059），（0.380±0.040）] decreased significantly（t=15.165，P=0.000；t=12.143，P=0.000），and the positive expression of Ki-67 in hippocampus decreased significantly（t=4.171，P=0.003）. Conclusion：SR induces the oxidative stress of brains and livers in mice and elevates the concentration of inflammatory cytokines in the brain and serum，and mediates the DNA damage through cell apoptosis.