Exploration Of The Mechanism By Which TLR7 Promotes The Release Of Inflammatory Mediators Leading To The Development Of POCD

Background and purpose of the study:Postoperative cognitive dysfunction(POCD)is a common central nervous system complication after surgical anesthesia,a neurologically impaired disease with impairments in memory,concentration and information processing ability and personality changes,commonly seen in elderly patients,with the most common in patients over 65 years of age.The main clinical manifestation is the decline in cognitive function(including learning,memory,mood,emotion,judgment,etc.)after surgical anesthesia and an increased risk of dementia.POCD not only increases the length of hospitalization and medical costs,but also leads to a decrease in social activity and seriously affects the quality of life.With the development of aging in China and globally and the increasing demand for quality of life,the active exploration of the pathogenesis of POCD has its important medical value and social significance for the prevention and treatment of POCD.There are many potential pathogenic mechanisms for postoperative cognitive dysfunction,among which the inflammatory hypothesis occupies an important place.Toll-Like Receptor 7(TLR7)is thought to be a factor that may play an important role in initiating the innate immune response in the central nervous system,and TLR7 induces a neuroinflammatory response in the brain by activating glial cells.TLR7 has also been found to exert some negative regulatory effects on cognitive function in animal models.However,the role of TLR7-induced neuroinflammation in affecting postoperative cognitive function needs to be further determined.This study will further explore the possible mechanisms by which TLR7 promotes inflammatory mediators leading to the development of POCD through bioinformatics analysis,clinical case validation,and microglial cell inflammation models.Methods:In this study,bioinformatics analysis of the GSE163943 dataset was performed to find the target genes associated with POCD.Patients who underwent general anesthesia for non-cardiac surgery in Jiangxi Cancer Hospital in 2021-2022 were selected and divided into POCD and non-POCD groups,preoperatively,within one week postoperatively for cognitive function assessment and ELSIA to detect blood TLR7,IL6,and TNF-α in the blood.Then an inflammation model of microglia was established,and the effect on the inflammation model was verified by knocking down TLR7 and detecting the level of IL6.Results:Bioinformatic analysis of the target gene of POCD was TLR7.The clinical study finally included 44 patients,16 in the POCD group and 28 in the non-POCD group.there were no statistical differences in the basic indexes between the POCD and non-POCD groups.TLR7,IL6,and TNF-α were significantly higher in the blood of patients in the POCD group compared with the non-POCD group(P<0.05).In the inflammatory model of microglia,IL6 was significantly decreased after knockdown of TLR7(p<0.001).Conclusion:In this study,we screened TLR7,which is closely associated with POCD,as a target gene by bioinformatics analysis,and verified that the blood levels of TLR7,IL6,and TNF-α were statistically significantly higher in patients with POCD compared to those with non-POCD by clinical samples.In a microglia model of inflammation,it was demonstrated that TLR7 can significantly suppress the inflammatory response by knocking down TLR7.Therefore,TLR7 may contribute to the development of POCD by promoting the release of inflammatory mediators.