Role Of SIRT1 Signaling Pathway In Dexmedetomidine Alleviating Postoperative Cognitive Dysfunction In Aged Rats

Objective:Dexmedetomidine?DEX?has the effect of reducing postoperative cognitive dysfunction?POCD?in the elderly population,this study established POCD model of aged rats to evaluate the role of silent information regulator 1?SIRT1?signaling pathway in dexmedetomidine alleviating postoperative cognitive dysfunction in aged rats.Methods:Ninety clean and healthy male Sprague-Dawley rats,aged 18²0 months and weighted 500⁷00 g,were selected and divided randomly into 5 groups?n=18?.Normal control group,POCD group,DEX group,DEX+EX527 group and EX527group.Dexmedetomidine at 25?g/kg was injected into rats intraperitoneally in DEX group and DEX+EX527 group at 30 min before operation.Meanwhile,the rats in Control group,POCD group and EX527 group were injected intraperitoneally with the same amount of normal saline.POCD group,DEX group,DEX+EX527 group and EX527 group were performed laparotomy 30 min later,and the operation time lasted for 30 min.DEX+EX527 group and EX527 group were injected with EX527 in the lateral ventricle before surgery.Control group was untreated.Six rats in each group were randomly selected for Morris water maze test at 1 day?T₁?,3 days?T₂?and 5 days?T₃?after operation to detect the escape latency and the frequency of crossing the original platform,immediately afterward,the rats were sacrificed and their hippocampus were taken out,then the levels of tumor necrosis factor-??TNF-??and interleukin-6?IL-6?in hippocampus of rats in each group were measured by ELISA.Western blotting was used to detect the expression of SIRT1,NF-?B,I?B,Bcl-2 and Bax in hippocampal neurons.Immunohistochemistry technique was used to obersve the expression of SIRT1 in hippocampal CA1 region of rats in each group.Detection of apoptosis of neuronal cells in hippocampal CA1 region by TUNEL.Malondialdehyde?MDA?content and total superoxide dismutase?SOD?activity in hippocampus of each group were detected by microplate reader.Results:?1?Compared with Control group,the escape latency in POCD group,DEX group,DEX+EX527 group and EX527 group was significantly prolonged,the frequency of crossing the original platform was decreased,the levels of TNF-?and IL-6 were significantly increased,SIRT1,I?B and Bcl-2 expression in hippocampal neurons was down-regulated,NF-?B and Bax expression increased,TUNEL positive cells increased,MDA content increased and superoxide dismutase activity was decreased?P<0.05?;?2?Compared with POCD group,the escape latency in DEX group was significantly shortened,the frequency of crossing the original platform was increased,the levels of TNF-?and IL-6 decreased,SIRT1,I?B and Bcl-2 expression of hippocampal neurons was up-regulated,NF-?B and Bax expression decreased in DEX group,TUNEL positive cells decreased,MDA content decreased and superoxide dismutase activity was increased?P<0.05?;there was no significant difference in the above indexes between DEX+EX527 group,EX527 group and group POCD?P>0.05?;?3?Compared with DEX group,the escape latency in DEX+EX527 group and EX527 group was significantly prolonged,the frequency of crossing the original platform was decreased,the levels of TNF-?and IL-6 were significantly increased,SIRT1,I?B and Bcl-2 expression of hippocampal neurons was down-regulated,NF-?B and Bax expression increased,TUNEL positive cells increased,MDA content increased and superoxide dismutase activity was decreased?P<0.05?.?4?Compared with DEX+EX527 group,there was no significant difference in the above indexes between EX527 group?P>0.05?.Conclusion:Surgical procedures can cause postoperative cognitive dysfunction in aged rats,which may be related to inflammatory response,apoptosis and oxidative stress;dexmedetomidine may attenuate postoperative cognitive dysfunction in aged rats,which may be related to SIRT1 signaling pathway.