Mechanism of spine pinching in behavioral improvement of autistic rats based on Nrf2/HO-1 pathway
Objective To investigate the mechanism of action of spine pinching in behavioral improvement of autistic rats from the perspective of oxidative stress and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)pathway.Methods The autism model rats were randomized into model group and spine-pinching group,with nine rats in each group.Nine normal rats were included as the blank group.In the spine-pinching group,spine-pinching manipulation was performed 21 times/d for consecutive 28 d.After the intervention,the rats in each group were sacrificed for sampling after behavioral tests.After perfusion and fixation,Nissl staining was performed to determine the neuronal damage in the CA1 and CA2 regions of the hippocampus,biochemical kits were applied to measuring the expressions of reduced glutathione(GSH),malondialdehyde(MDA),superoxide dismutase(SOD),and catalase(CAT)in the hippocampus,and Western blot was used to examine expressions of Nrf2 and its phosphorylation indicators p-Nrf2,HO-1,and NAD(P)H:quinone oxidoreductase 1(NQO1).Results Compared with the blank group,the model group exhibited significantly lower social index and standing frequency(P<0.01),as well as a significant increase in grooming frequency(P<0.01).Compared with the model group,the spine-pinching group showed a significant improvement in social index and standing frequency(P<0.01),with a reduction in grooming frequency(P<0.05).In the blank group,the neurons were closely arranged,morphologically regular,and abundant in Nissl bodies.However,in the model group,a large number of neurons were damaged,with pyknotic and deeply stained nuclei,ruptured cell membranes,blurred cell boundaries,displaced and dissolved Nissl bodies,and a decrease in the number of Nissl-positive cells.In the spine-pinching group,cells were basically arranged neatly,with relieved nuclear pyknosis,acceptable cellular morphology,and an increase in the number of Nissl-positive cells.Compared with the blank group,GSH,SOD,CAT,p-Nrf2/Nrf2,HO-1,and NQO1 expressions in the model group decreased(P<0.05 or P<0.01),and MDA expression significantly increased(P<0.01).Compared with the model group,GSH,SOD,CAT,p-Nrf2/Nrf2,HO-1,and NQO1 expressions were higher(P<0.05 or P<0.01)and MDA expression was significantly lower(P<0.01)in the spine-pinching group.Conclusion Spine pinching can improve the behaviors of rats with autism,the mechanism of which is related to activating the Nrf2/HO-1 pathway,inducing the expressions of antioxidant factors,relieving oxidative stress,and reducing of the neuronal damage.
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