A Research Of The S100?/RAGE Pathway Resulting In Sepsis-associated Encephalopathy

Objective:To explore the occurrence of neuroinflammatory response pathway in sepsis-associated encephalopathy by detecting the levels of S100?,RAGE,IL-1? and TNF? in the brain tissue of mice with septic encephalopathy,in order to provide a new therapeutic direction for the treatment of septic encephalopathy.Methods:(1)With the method of random number,We averagely divided 50 C57BL/6 mice into 4 groups :control group,sepsis-associated encephalopathy group(SAE group),sepsis-associated encephalopathy + pentamidine group(pentamidine group).sepsis-associated encephalopathy + FPS-ZM1 group(FPS-ZM1 group),sepsis-associated encephalopathy + pentamidine + FPS-ZM1 group(Pentamidine+ FPS-ZM1 Group).(2)The mouse model of sepsis-associated encephalopathy was constructed.(3)We injected pentamidine from the intracerebroventricle in the Pentamidine Group and implemented intraperitoneal injection of FPS-ZM1 in the FPS-ZM1 group.SAE group and control group were not intervened.(4)All C57BL/6 mice were executed.Then the brain tissue was separately removed and homogenized.(5)The levels of S100? and RAGE were detected by Western blotting in each group.The levels of IL-1? and TNF? were detected by enzyme-linked immunosorbent assay(ELISA).(6)ANOVA was performed for each group of quantitative data by the software of spss 22 nd edition.P<0.05 was considered statistically significant.Results:(1)The s100? content in the SAE group was significantly higher than that of the other groups(2.21±0.03,p<0.01);The s100? content in the Pentamidine+ FPS-ZM1 group(1.14±0.05)was significantly lower than that in the Pentamidine group and the FPS-ZM1 group(p <0.01);There was no significant difference in the s100? content between the Pentamidine group(1.57±0.08)or the FPS-ZM1 group(1.51±0.05)(P>0.05).(2)The RAGE content of the SAE group was significantly higher than that of the other groups(2.23±0.08,p<0.01);the RAGE content of the Pentamidine group(1.94±0.04)was significantly higher than that of the FPS-ZM1 group(1.21±0.14),p <0.01;There was no significant difference in the RAGE content between the Pentamidine+ FPS-ZM1 group(1.15±0.10)and the FPS-ZM1 group(P>0.05).(3)The IL-1? content in the SAE group(92.91 pg/ml±2.83 pg/ml)was significantly higher than that in the Control group(23.01 pg/ml±2.34 pg/ml)and the Pentamidine group(69.11 pg/ml±2.31 pg/ml),P<0.01;The IL-1? content in the Pentamidine group(69.11 pg/ml±2.31 pg/ml)was significantly higher than that of the FPS-ZM1 group(49.60 pg/ml±1.07 pg/ml),P<0.01;There was no significant difference in the IL-1? content between the FPS-ZM1 group(49.60pg/ml±1.07pg/ml)and the Pentamidine+FPS-ZM1 group(48.35 pg/ml±2.77 pg/ml),P>0.05.(4)The TNF? content of the SAE group(275.91 pg/ml±5.76 pg/ml)was significantly higher than that of the Control group(78.04 pg/ml±2.30 pg/ml)and the Pentamidine group(195.68 pg/ml±4.54 pg/ml),P<0.01;the TNF? content of the Pentamidine group(195.68 pg/ml±4.54 pg/ml)was significantly higher than that of FPS-ZM1 group(143.57 pg/ml±3.33 pg/ml),P<0.01;There was no significant difference in the TNF? content between the FPS-ZM1 group(143.57 pg/ml±3.33 pg/ml)and Pentamidine+FPS-ZM1 group(148.74 pg/ml±1.91 pg/ml),P>0.05.Conclusion:1.The occurrence of sepsis causes an increase in the level of S100? content of the brain tissue,which in turn leads to a neuroinflammatory reaction through the S100?/RAGE pathway.It causes the occurrence of SAE.2.The neuroinflammatory response caused by SAE can be significantly alleviated,by inhibiting the production of s100? and RAGE in brain tissue.