To Investigate Effects And Mechanism Of Endoplasmic Reticulum Stress In The Cerebral Blood Supply After Depression

[Abstract] Obiective:To Investigate effect and machnisms of Antioxidants by metoprolol, N-acetyl cysteine and escitalopram in the process of major depressive disorder, abserve concentration of NOS?NO?MAD?SOD and the expression of eNOS?GRP78?CHOP?Caspase-12 by rt-PCR and western blot on the oxidative stress in hippocampus and prefrontal cortex of rat with chronic unpredictable mild strss. Mrethods 45 SD rats were were randomly divided into five groups:control group,model group, metoprolol group, N-acetyl cysteine group and escitalopram group,9 rats in each groups.The rats were exposed to the chronic unpredictable mild strss(CUMS) and isolation to create a depression model.Open field test and sucrose water consumption test were performed to observe the behavior of animals after injection administration with drugs (as 10 mg/kg/d for metoprolol,125mg/kg/d for N-acetyl cysteine and 10mg/kg/d for escitalopram) or saline water(as 10 mg/kg/d for CUMS group) for 21 days.The levels of apoptohage in hippocampad and prefrontal cortex neurons cells were detected by flow cytomestry. The expression of eNOS,GRP78,CHOP,Caspase-12 mRNA was measured with RT-PCR,the protein expression of eNOS, eNOS-ser1179,GRP78,CHOP,Caspase-12 was detected by Western blot.The concentration of NOS?NO?SOD?MDA was detected by microplate. Results 1.Compared with the control group, the model group were lower significantly in Open field test and sucrose water consumption test and showed decreased in weight and the levels of apoptohage(P<0.05). The three drugs groups were significantly higher than model group(P<0.05).2.The apoptosis result showed that compared with the control group, the CUMS group were higher significantly in apoptosis rates,N-acetyl cysteine group and escitalo pram group were significantly lower than CUMS group (P<005) 3.The results tested ni croplate reader shows that compared with the control group, the activity NOS, the concentration MDA and NO were higher,the activity of SOD were lower significantly in CUMS group. Compared with the CUMS group the activity NOS, the concentration MDAand NO were lower,the activity of SOD were higher significantly in the metoprolol group, N-acetyl cysteine group and escitalopram group,the Differences are statistically both in the hippocampus and cortex(P<0.05).4. The results of rt-PCR showed that, compared with the control group the exprsession of eNOS were lower, the Caspase12, GRP78 and CHOP were higher in CUMS group in hippocampus. Compared with the CUMS group the exprsession of eNOS were higher,the Caspasel2, GRP78 and CHOP were lower in N-acetyl cysteine group and escitalopram group (P<0.05).5.The results of Western Blot showed that, compared with the control group the exprse ssion of eNOS and eNOS-ser1179 were lower, the Caspasel2, GRP78 and CHOP were higher in CUMS group (P<0.05). Compared with the CUMS group the exprsession of eNOS and eNOS-ser1179 were higher,the Caspasel2, GRP78 and CHOP were lower in N-acetyl cysteine group and escitalopram group (P<0.05). Conclusions 1. The behavioral score and weight reduction of the depression group, Mei TORO M, NAC, Ai Sciplan can improve the Depression Behavior of rats.. depression rats in hippocampus and cerebral cortex apoptosis rate increased under electron microscope observation of nerve cells and capillary damage, NAC and escitalopram can reduce the rate of cell apoptosis in rats with and improve the rat nerve cell swelling and capillary damage. Oxidative stress indexes of MDA and no content and NOS activity increased. Depression in rat brain tissue and SOD activity decreased, metoprolol, NAC and escitalopram can reduce the level of MDA, no, NOS and SOD activity increased, depression rat brain endothelial nitric oxide synthase eNOS expression and decreased, endoplasmic reticulum stress related protein GRP78, caspasel2 and chop relative expression increased, metoprolol, NAC and escitalopram can increase in eNOS expression, NAC and escitalopram can reduce brain tissue in endoplasmic reticulum stress related protein GRP78, caspasel2 and chop expression.