The Mechanism Study Of FGF22 Moderating IL-1? On Suppressing The Apoptosis Of Hippocampal Cell In Depression

Objective1.To investigate the variation of serum Fibroblast growth factor 22?FGF22?of first episode depressive patients before and after treatment and the relationship with interleukin-1??IL-1??and Hamilton's depression scale?HAMD?,in order to provide assistance for the further study of the pathogenesis of depression.2.The chronic unpredictable mild stress?CUMS?depression model of rat were established and primary hippocampal cells were cultured to study the changes of IL-1?and FGF22,depressive behaviors and apoptosis of hippocampal neuronal cells.The aim of this study was to clarify the relationship between FGF22 and IL-1?in the hippocampus of depression and the regulation of FGF22/IL-1?pathway on apoptosis of primary hippocampus in depression,which provides more theoretical basis for the pathogenesis of depressive disorderMethods1.Ninety patients with first-episode depression were collected in clinical work and treated with paroxetine for 8 weeks.The levels of serum FGF22 and IL-1?were measured by ELISA before and after treatment,and the HAMD scale was also evaluated.The correlation analysis was performed.At the same time,90 healthy volunteers were collected as control group.All datum above data were statistically analyzed.2.Totally 36 male SD rats were randomly selected from 60 male SD rats,and were divided into 6 groups including nature control?NC?group,CUMS group,CUMS group with lentivirus negative control?CUMS+Mock¹?,CUMS group with lentivirus-mediated-FGF22 injection?CUMS+FGF22?,CUMS group with Mock²injection?CUMS+Mock²?and CUMS group with IL-1ra injection?CUMS+IL-1ra??n=6 for each group?.The contents of the observation are as follows:?Body weight,open field test and forced swimming test were used to observe the behavioral changes of NC group and CUMS group in order to evaluate the success of the establishment of depression model.?Behavioral tests were used to evaluate the depressive behavior of rats in CUMS group,CUMS+Mock¹ group and CUMS+FGF22 group and western blot and immunohistochemical staining were used to detected the changes of IL-1?and apoptosis in hippocampus in these groups.?Behavioral tests were used to evaluate the depressive behavior of rats in CUMS group,CUMS+Mock² group and CUMS+IL-1ra group and western blotwere used to detected the changes of apoptosis in hippocampus in these groups.The other 24 rats were sacrificed on a weekly basis?six rats per week?,and the time-variations of FGF22 and IL-1?in hippocampus were detected by western blot.3.Primary cultured hippocampal neuronal cells of rats were randomly divided into control group,100?g/l FGF22 group and 200?g/l FGF22 group.After 24h of cell culture,IL-1?,Bcl-2 and Bad protein levels were detected by Western blot,and apoptosis of cells were detected by AnnexinV/PI flow cytometry.Results1.The levels of serum FGF22 in first episode depression group were significantly lower than that of the healthy control group(180.44±17.02 vs 200.74±16.63,t_?179?=8.090,P<0.01),and the levels of serum IL-1?were significantly higher than that in healthy control group(11.23±1.89 vs 5.22±1.60,t_?179?=23.02,P<0.01).The differences were all statistically significant.2.After antidepressant treatment,the levels of serum FGF22 in patients with depression were significantly higher than that before treatment(180.44±17.02 vs195.74±19.57,t_?179?=13.18,P<0.01),and the levels of serum IL-1?were significantly lower than that before treatment(11.23±1.89 vs 8.16±1.50,t_?179?=15.82,P<0.01).The differences were all statistically significant.3.The correlation analysis showed that serum FGF22 levels were negative correlated with HDRS scores?r=-0.691,P<0.01?and serum IL-1?levels?r=-0.685,P<0.01?.Meanwhile,serum IL-1?levels were positively correlated with HDRS scores?r=0.749,P<0.01?.4.Four weeks after modeling by CUMS method,we examined our CUMS paradigm by assessing its impact on three well-established parameters of depression-like behaviours in rodents.Finally,we proved that CUMS is a good method to establish the depression model.5.During the 4 weeks of establishing our CUMS models,we found that CUMS induced decreased FGF22 expression in the hippocampus with exposure to stress in a time-dependent manner,while IL-1?expression in the hippocampus increased?P<0.05 or P<0.01?.6.HippocampalFGF22overexpressionalleviatedCUMS-induced depression-like behaviour and apoptosis in the hippocampus;FGF22down-regulates IL-1?protein expression in hippocampus;Intra-hippocampal delivery of IL-1ra alleviated CUMS-induced depression-like behaviour and apoptosis in the hippocampus?P<0.05 or P<0.01?.7.FGF22 treatment downregulated the expression of IL-1?and alleviated apoptosis in primary hippocampal neuronal cells induced by FGF22 in a dose-dependent manner.The effect of 200?g/l FGF22 group was more obvious than that of 100?g/l FGF22 group?P<0.05 or P<0.01?.Conclusion1.Among the first episode depressive patients,the level of serum FGF-22 was abnormal,and it could be a better indicator of peripheral blood in response to depression,which plays an important role in the pathogenesis of depression.2.FGF22 can play an antidepressant and antiapoptotic of hippocampus role by reducing the expression of IL-1?in hippocampal cells,which further reveals the pathogenesis of depression.It provides more experimental evidence for the cross fusion of neurotrophic theory and inflammatory theory.