Apelin Attenuates Depressant-like Behavior And Oxidative Stress In Chronic Stress Co-treated With LPS Rats

[Backgroud and Objective] Depression is a neuropsychiatric disorder.The main symptoms of depression contain feelings of sadness,loneliness and guilt,lack of enthusiasm,sleep disorders,and self-contempt.14% people worldwide suffer from depression.It is of great significance to study the pathogenesis of depression and to find new antidepressants.Animal studies have found that microglia and astrocytes in depressive rats were activated,and the expression of oxidative stress factors is significantly increased.These results suggest that oxidative stress may be one of the important mechanisms of depression.Apelin is a natural ligand of G protein coupled receptor APJ.The localization of APJ in the marginal structure suggests that Apelin may play an important role in emotional processes.Previous studies in our laboratory have shown that Apelin has antidepressant effects in various depressive models.But the anti-depressive mechanism and anti-depressant effect of Apelin-13 whether due to the expression of oxidative stress it is still unknown.This study investigated whether Apelin-13 ameliorates the depressive behavior induced by chronic unpredictable stress and LPS through oxidative stress.[Methods] In this experiment,we observed the depressive behavior induced by co-treatment of UCMS and LPS in rats.We used sugar water preference test,forced swimming and adrenal weight ratio to evaluate the effect of Apelin-13 on depressive behavior induced by co-treatment of UCMS and LPS in rats.Western Blot was used to detect the expression of IBA-1 and GFAP in hippocampus to observe the effect of Apelin-13 injection on the activation of microglia and astrocytes induced by co-treatment of UCMS and LPS in rats.Western blot was used to detect the expression of oxidative stress regulatory factor(NRF2)in hippocampus to evaluate the effect of intraventricular injection of Apelin-13 on co-treatment of UCMS and LPS induced oxidative stress regulatory factors in rats.The changes of the expression of oxidative stress factors ROS,i NOS and n NOS in hippocampus were examined by Western Blot to evaluate the effects of Apelin-13 on oxidative stress factors in rats induced by co-treatment of UCMS and LPS.The changes of mitochondrial mitofilin protein expression in hippocampus were detected by Western Blot to evaluate the effect of Apelin-13 injection on oxidative stress induced by co-treatment of UCMS and LPS in rats.[Results] Combined effects of UCMS and LPS lead to a depressive behavior in rats.Apelin-13 improve the adrenal weight ratio caused by the co-treatment of UCMS and LPS.Apelin-13 improve the expression of IBA-1 and GFAP in rats induced by co-treatment of UCMS and LPS.Apelin-13 improve the expression of NRF2 in rats induced by co-treatment of UCMS and LPS.The co-treatment of UCMS and LPS improve the expression of oxidative stress factor such ad ROS,i NOS and n NOS in hippocampus of rats.Apelin-13 improve the expression of mitochondrial mitofilin protein in hippocampus induced by co-treatment of UCMS and LPS.[Conclusion] Apelin-13 improve the depressive behavior and oxidative stress induced by co-treatment of UCMS and LPS in rats.