Correlation Between ProBDNF And Its Pathway Protein TPA With Depressive Episode

Objectives:The Brain-Derived Neurotrophic Factor(BDNF)hypothesis in patients with depressive episode has been a research hotspot for a long time.Tissue Plasminogen Activator(tPA)may participate in the pathophysiological process of depressive episode by affecting the cleavage of Brain-Derived Neurotrophic Factor Precursor(pro BDNF).This study will start from the tPA-pro BDNF pathway to explore the differences in the concentration of peripheral blood pro BDNF and the expression of Messenger RNA(m RNA)and protein of tPA in lymphocytes between patients with depressive episode and healthy controls.To explore the changes of plasma pro BDNF and lymphocyte tPA m RNA and protein levels in patients with depressive episode before and after treatment,conduct correlation analysis,explore the relationship between pro BDNF,tPA,and depressive episode,and provide the experimental basis for clarifying the pathogenesis or biological indicators and therapeutic targets of depressive episode.Methods:Peripheral blood samples were collected from a healthy control group meeting the inclusion criteria and patients with depressive episode before and after treatment.Age,gender,ethnicity,and marital status of the depressive episode group were matched with those of the healthy control group.Enzyme-linked Immuno Sorbent Assay(ELISA)was used to detect the concentration of pro BDNF in peripheral blood,and Quantitative Real-Time PCR(Q-PCR)was used to detect the expression level of tPA m RNA in peripheral lymphocytes.Western Blot(WB)was used to detect the expression level of tPA protein in peripheral lymphocytes.The 24-Item Hamilton Depression Rating Scale(HAMD-24)was used to evaluate the severity and efficacy of patients with depressive episode.Statitstic Package for Social Science(SPSS)25.0statistical software was used for analysis.Results:1.A total of 33 patients with depressive episode who received antidepressant treatment for 4 weeks were collected(baseline depression group before treatment and depression treatment group after 4 weeks).And 33 cases in healthy control group.2.Compared with the healthy control group,the concentration of pro BDNF in peripheral blood of baseline depressive episode group was significantly increased,and the difference was statistically significant(t=-3.165,P < 0.01);There was no significant difference in tPA m RNA in peripheral blood lymphocytes(Z=-1.058,P >0.05).The expression level of tPA protein in baseline depression group was lower than that in healthy control group,but the difference was not statistically significant(Z=-0.898,P > 0.05).3.The HAMD-24 score of the depressive episode group before and after treatment(baseline and 4 weeks after treatment)was lower after treatment than before treatment(t=27.25,P < 0.001),indicating that antidepressant treatment is effective;The expression of pro BDNF concentration after treatment was down-regulated compared with that before treatment(t=-2.053,P < 0.05),and the expression of tPA m RNA before and after treatment had no significant change(Z=-0.009,P > 0.05).The expression level of tPA protein after treatment was significantly higher than that before treatment(Z=-3.046,P < 0.01).4.HAMD-24 score was positively correlated with pro BDNF concentration in the baseline depressive episode group(r=0.397,P < 0.05);HAMD-24 score was negatively correlated with tPA protein expression level(r=-0.626,P < 0.001).The expression level of tPA protein was negatively correlated with the concentration of pro BDNF(r=-0.380,P < 0.05).The reduction rate of HAMD-24 before and after antidepressant treatment was positively correlated with the reduction rate of pro BDNF(r=0.611,P < 0.001).5.In ROC curve analysis,the concentration of pro BDNF in peripheral blood had a certain diagnostic value for depressive episode(AUC=0.694,P < 0.01).Conclusion:1.pro BDNF may be involved in the pathophysiological mechanism of depressive episode,and the concentration of pro BDNF in peripheral blood can reflect the severity of the condition of patients with depressive episode to a certain extent.2.Antidepressant treatment can alleviate depressive symptoms by reversing the expression level of pro BDNF.pro BDNF is expected to become a therapeutic drug target,and pro BDNF may be used as an evaluation indicator of the therapeutic effect of patients with depressive episode.3.tPA can participate in the occurrence and development of depressive episode by affecting the expression of pro BDNF,and antidepressant treatment may alleviate depressive symptoms by reversing the expression of tPA.4.There was no significant difference in the expression level of tPA m RNA among all groups,which was not consistent with the expression level of peripheral blood protein,which may be related to the influencing factors of tPA activity(inhibitor or activator).