H₂S Improvespostoperative Cognitive Dysfuction Involving Inhibitions Of Esendoplasmic Reticulum Stress And Neuroinflammation In Hippocampus

[Backgroud and Objective]Postoperative cognitive dysfunction?POCD?has always been found in elderly patients,but its mechanisms and the way to prevent and treat POCD is unclear.It has been reported that endoplasmic reticulum stress and neuroinflammation in hippocampus are involved in learning and memory dysfunction and that hydrogen sulphide?H₂S?has play an important role in regulating learning and memory.So,aged?18–20 months?male rats were subjected to laparotomy surgery to establish the model of POCD,which was to detect?1?whether POCD involves the disturbance of H₂S generation and/or the increases in endoplasmic reticulum stress and neuroinflammation in the hippocampus of aged rats;?2?whether H₂S alleviates POCD and whether its mechanism is involved in reducing endoplasmic reticulum stress and neuroinflammation in hippocampal of aged rats[Methods]Morris water maze?MWM?,novel object recognition,and Y-maze tests were used to detect the cognitive function of rats.The level of H₂S in the hippocampus was measured by Unisense H₂S sensors.The expressions of two key enzymes for generation of endogenous H₂S(3-mercaptopyruvatesulphurtransferase?3-MST?proteinsand Cystathionine-bata-synthase?CBS?,and the marker proteins of endoplasmic reticulum stress?Bip and Cleaved caspase-12?were detected by Western Blot.The contents of proinflammatory cytokines?IL-1?,IL-6and TNF-??in hippocampus of rats were determined by ELISA.The number of macrophages?CD45⁺?and activated astrocytes?IBA-1⁺?in hippocampus were detected by immunofluorescence assay.[Results]1.After laparotomy surgery for 3 days,the cognitive functions of aged rats were detected by Y-maze,novel object recognition and Morris water maze tests.Results show that in the postoperative aged rats,the alternation performance in Y-maze test and the new object recognition index in NORT test is reduced,the escape latency is increase since the third-day in acquisition phase of the MWM test,the across times in the platform quadrant in probe trial of MWM test is decrease.Those results indicated that the postoperative aged rats are in possession of cognitive dysfunction.In addition,the levels of CBS and 3-MST and the content of H₂S in the hippocampus of postoperative aged rat is decrease.Notably,excessive endoplasmic reticulum?ER?stress and neuroinflammatory were detected in the hippocampus of postoperative aged rats,as indicated by the upregulation of Bip and Cleaved caspase-12 as well as the increases in the contents of proinflammatory cytokines?IL-1?,IL-6 and TNF-??and the number of macrophages and activated astrocytes,respectively.2.After pretreated with NaHS?30 and 100?mol/kg/d,i.p.?for 2 w,aged rats were subjected to laparotomy surgery.Three days after operation NaHS?100?mol/kg?increased the alternation performance of POCD rats in Y-maze test,improved the new object recognition index of POCD rats in NORT test,reduced the escape latency of POCD rats since the third-day of acquisition phase of MWM test,and increased the spending time and across times in the platform quadrant of probe trial in MWM test.These results indicated that H₂S alleviates cognitive dysfunction in POCD rats.In addition,NaHS?100?mol/kg?markedly down-regulated the expressions of Bip and Cleaved caspase-12 proteins as well as the levels of proinflammatory cytokines?IL-1?,IL-6 and TNF-??and the number of macrophages and activated astrocytes in the hippocampus of POCD rats.[Conclusion]1.The postoperative cognitive dysfunction is invovled in the disturbance of H₂S generation as well as the increases in hippocampal endoplasmic reticulum stress and neuroinflammation.2.H₂S attenuates the postoperative cognitive dysfunction and the mechanisms are involved in the inhibition of endoplasmic reticulum stress and neuroinflammation in the hippocampus of POCD rats.