Stress Injury Related Signal Chain And Immune Injury Mechanism Research Of Mental Illness

Objective:To explore the signal chains in stress injury and the mechanisms of immunologic injury in patients with psychotic diseases.Methods:The research included two parts,1) We established rat model of middle cerebral artery occlusion (MCAO) as an injury stress model. Immunohistochemical technique was used to analyse the expression of the injury and related repairing signals (IL-1β、IL-6、 TNF-α、MMP-9、ICAM-1、MCP-1、TGF-β) in rats damaged brain, and ELISA was used to detect the levels of correlative signals (IL-1β、TNF-α、IL-6、HSP70、ACTH) in the rats serum.2)Serum IL-1β、IL-6、IL-17A、sIL-6R、sgp130were measured in patients with Tourette’s syndrome、schizophrenia、disturbance of emotion(depression) and control groups, ELISA was simultaneously used to explore the antinuclear antibody(ANA) and anti-brain antibody in the serum of patients and control groups.Results:1)In the damaged brain regions of rats, all the injury and related repairing signals including modulating signals(IL-1and IL-6)、effect molecules(TNF-α、MMP-9)、 inflammation cell adhesion molecule (ICAM-1) and chemokine (MCP-1)、repairing factor(TGF-β) showed elevated levels and expressed two peaks. It is that they expressed the first peak after ischemia/reperfusion (IR)24h to48h, and then slightly decreased; the second peak appeared after IR72h/96h. The second peak related to repairing process is always higher than the first peak.2)The elevated patterns of all the rats’serum signals (IL-1β、IL-6、TNF-α、HSP70、 ACTH) which also showed two peaks were similar to the signals’pattern in damaged brain regions.3)Serum expression of immune injury related factors and antoantibodies were measured in patients and control groups, the results were as follows:serum levels of IL-1β、 IL-6、IL-17A、sgp130were all significantly higher in patients with schizophrenia、 depression and Tourette’s syndrome than control group. The expression of IL-1βand sgp130in patients with schizophrenia、depression and Tourette’s syndrome were more than the normal group, the expression of IL-6in patients with schizophrenia and depression were higher than control group, the concentration of IL-17A were higher in patients with schizophrenia and Tourette’s syndrome than control group. Correlation analysis showed that there were positive relationship between IL-1βand IL-6(R=0.449, p<0.01),sIL-6R and sgp130(R=0.497, rp<0.01) in patients with schizophrenia; also in patients with depression between IL-1β and IL-6(R=0.434, p<0.01). IL-1β and IL-17A(R=0.353, p<0.05), there was positive trend between IL-6and sIL-6R(R=0.215, p>0.05); in patients with Tourette’s syndrome, IL-1β/IL-6(R=0.776,p<0.01) and sgp130/IL-6(R=0.341,p<0.05) existed positive relationships.4)The expressions of autoantibodies ANA and ABAb in patients with Tourette’s syndrome had much higher positive rate than in normal people, and the rates both showed statistical differences(51.3%vs25%,66.7%vs2.5%, p<0.01). Moreover, there was negative correlation between ABAb and sgp130(R=0.375, p<0.05).Conclusion:1)During ischemia/reperfusion, all the injury and related repairing signals both in CNS and serum expressed higher than normal status, which indicated that DAMP initiated the stress response and repairing signals of the organisms, neuro-endocrine-immune regulation network coordinate injury response either in local tissues or of the systemic process.2)Immune injury related factors those DAMP initiated expressed higher in serum of psychotic patients than healthy people, and antoantibodies also existed higher positive rates in patients with Tourette’s syndrome, all those results revealed that mechanisms of immune injury,specially autoimmune damage mechanism may participate in the progress of psychosis.