Relationship Between NLRP3 Inflammasome And Early Cognitive Impairment After Hip Replacement In Elderly Patients

[Background]Postoperative cognitive dysfunction(POCD)is the main clinical manifestation of impaired learning and memory ability after surgery or anesthesia,which is common in elderly patients.The latest data shows that the incidence of POCD in elderly patients is about 25%to 40%.Although the US Postoperative Cognitive Research Collaboration Group in November 2018 recommended that POCD be renamed Perioperative Neurocognitive Disorder(PND),the concept of PND involves a wide range,and most studies currently still use the concept of POCD.In recent years,studies have confirmed that IL-1?-mediated peripheral inflammatory response plays an important role in the pathogenesis of POCD,but the specific induction mechanism is still unclear.The latest research confirms that Inflammasome as an intracellular pattern recognition receptor plays an important role in regulating IL-1? synthesis and release.At present,there are four main known inflammatory bodies,namely NLRP1 inflammatory body,NLRP3 inflammatory body,IPAF inflammatory body and AIM2 inflammatory body,among which the most relevant to IL-1? synthesis and secretion is NLRP3 Inflammatory body.The NLRP3 inflammatory body is a complex composed of multiple proteins,which can regulate the innate immune system to sense the stress response and cleave it into mature Caspase-1 by activating pro-Caspase-1,Caspase-1 continues to act on the IL-1?precursor pro-IL-1? to turn it into an active mature body with an inflammatory response,and more and more evidence shows that the activation of NLRP3 inflammatory bodies and neurodegeneration Sexual diseases.a7 nicotinic acetylcholine receptor(a7nAChR)is mainly distributed on the cell membrane and mitochondrial outer membrane of microglia and astrocytes in the brain,as an important receptor for cholinergic anti-inflammatory pathway,Plays an important role in the anti-inflammatory pathway.Studies have shown that central cholinergic deficiency is related to age-related cognitive impairment,and activation of the cholinergic anti-inflammatory pathway mediated by a7nAChR can alleviate neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis.Several studies have reported that a7nAChR may affect the expression of inflammatory mediators in the body by regulating NLRP3 inflammatory bodies.We have found in the previous basic research that agitation of a7nAChR can alleviate POCD in elderly rats,but there is still no basic clinical research on this receptor and postoperative cognitive impairment.[Objective]This study mainly explored the role of a7nAChR and NLRP3 inflammatory bodies in peripheral blood mononuclear cells in early postoperative cognitive impairment caused by hip replacement in the elderly.[Methods]1.Use the MMSE scale,Hopkins speech learning test-correction method,brief visual spatial memory test-correction method,digital connection test,digital memory breadth test,digital-symbol mode test to perform preoperative and postoperative patients who meet the test criteria Three-day cognitive function assessment,according to the score results,it was divided into early postoperative cognitive impairment group(group A)and non-postoperative early cognitive impairment group(group B);2.Collect the patient's general data and related intraoperative detection indexes,and collect the patient's peripheral blood before and after the operation and perform RT-PCR experiment to determine NLRP3,IL1-?,caspase-1 and a7nAChR groups in monocytes.[Results]1.According to the cognitive scale,there were 15 patients with cognitive impairment 3 days after surgery,with an incidence of 28.85%(15/52),which was consistent with the results reported in previous studies.Therefore,it was divided into 2 groups,early postoperative cognitive impairment group(group A,n=15)and early postoperative cognitive impairment group(group B,n=37).2.Compare the general condition of the two groups of patients(such as age,gender,age,education level),laboratory results(such as monocyte count,neutrophil count,uric acid value,electrolyte disorder,etc.),transcranial Doppler There was no statistically significant difference in results,intraoperative blood loss,fluid replacement,application of bone cement,and length of operation(P>0.05).3.The peripheral blood of patients was collected before operation and after operation to isolate monocytes and further tested by RT-PCR:3.1 Preoperative general data(gender,ASA grade,age,weight,and education level)of patients in groups A and B,as well as surgery-related data(operation time,blood loss,fluid input,whether bone cement,anesthetic drugs,and other drug doses,etc.)In comparison,the difference was not statistically significant(P>0.05).3.2 The expressions of NLRP3 mRNA,IL1-? mRNA and caspase-1 mRNA in peripheral blood mononuclear cells of group A were significantly higher than those before operation,the difference was statistically significant(P<0.05);The expressions of NLRP3 mRNA,IL1-? mRNA,and caspase-1 mRNA in blood mononuclear cells were not significantly different from those before surgery(P>0.05),as shown in Figures 1,2 and 3.3.3 In group A,the expression of a7nAChR mRNA in peripheral blood monocytes was significantly lower than that before operation,and the difference was statistically significant(P<0.05);in group B,the expression of a7nAChR mRNA in peripheral blood monocytes after operation was not significantly higher than before operation The difference(P>0.05)is shown in Figure 4.[Conclusion]1.The upregulation of NLRP3 inflammatory bodies of monocytes caused by surgery and anesthesia may play an important role in the peripheral inflammatory response to early postoperative cognitive impairment.2.Surgery and anesthesia inhibit the expression of a7nAChR in peripheral monocytes may be a potential upstream factor for the overexpression of NLRP3 inflammatory bodies.The a7nAChR-NLRP3 inflammatory body-IL-1? signal axis may be a potential intervention target for early postoperative cognitive impairment.