Effect of Remifentanil on Hemodynamics and Memory Function in Mice Undergoing Hemorrhagic Shock Resuscitation Through the TXNIP/NLRP3/Cspase-1 Signaling Pathway

LI Xinghui; LEI Dingcai; ZHAO Wei

doi:10.13730/j.issn.2097-2148.2025.09.003

Abstract：Objective To investigate the impacts of remifentanil on hemodynamics and memory function in mice with hem-orrhagic shock resuscitation(HSR)through the thioredoxin interacting protein(TXNIP)/nucleotide binding oligomerization do-main like receptor protein 3(NLRP3)/cysteinyl aspartate specific proteinase1(Caspase-1)signaling pathway.Methods A total of 72 C57BL/6 male mice were randomly divided into sham operation group(inject an equal amount of normal saline into the tail vein),model group(inject an equal amount of normal saline into the tail vein),remifentanil low-dose group(tail vein injection of 4 mg/kg remifentanil+equal amount of normal saline),remifentanil high-dose group(tail vein injection of 8 mg/kg remifentanil+equal amount of normal saline),remifentanil high-dose+empty lentivirus(pLVX-NC)group(tail vein injection of 8 mg/kg remifentanil+2.5 μl pLVX-NC)and remifentanil high-dose+TXNIP overexpression lentivirus(pLVX-TXNIP)group(tail vein injection of 8 mg/kg remifentanil+2.5 μl pLVX-TXNIP)with 12 mice in each,according to the random number table method.The mice in the sham operation group were only punctured without exsanguination,and HSR models were estab-lished in all groups except the sham operation group.The learning and memory functions of mice were tested by water maze;the mean arterial pressure(MAP),heart rate(HR),diastolic blood pressure(DBP),systolic blood pressure(SBP)of mice in each group were measured by color Doppler ultrasound;cell apoptosis were detected by terminal deoxynucel neotidyl transferas-media-ted dUTP nick end labeling(TUNEL)method;the content of malondialdehyde(MDA),activities of superoxide dismutase(SOD)and catalase(CAT)in mice hippocampal tissues were detected by colorimetry;the expression of TXNIP/NLRP3/Caspase-1 pathway proteins were detected by Western blot.Results Compared with the sham operation group,the escape laten-cy,apoptotic cell positivity rate,MDA content,TXNIP,NLRP3 and Caspase-1 protein expressions of mice in model group sig-nificantly increased(all P＜0.05);times of passed through the original platform,MAP,HR,DBP,SBP and the activities of SOD and CAT significantly decreased(all P＜0.05).Compared with the model group,the escape latency,apoptotic cell positivi-ty rate,MDA content,TXNIP,NLRP3 and Caspase-1 protein expressions of mice significantly decreased in remifentanil low-dose and high-dose groups(all P＜0.05);times of passed through the original platform,MAP,HR,DBP,SBP and the activi-ties of SOD and CAT significantly increased(all P＜0.05).Compared with the low-dose remifentanil group,the escape latency,apoptotic cell positivity rate,MDA content,TXNIP,NLRP3 and Caspase-1 protein expressions of mice in remifentanil high-dose group significantly decreased(all P＜0.05);times of passed through the original platform,MAP,HR,DBP,SBP and the ac-tivities of SOD and CAT of mice significantly increased(all P＜0.05).Compared with the remifentanil high-dose and remifentanil high-dose+pLVX-NC group,the escape latency,apoptotic cell positivity rate,MDA content,TXNIP,NLRP3 and Caspase-1 protein expressions of mice in remifentanil high-dose+pLVX-TXNIP group significantly increased(all P＜0.05);times of pas-sed through the original platform,MAP,HR,DBP,SBP and the activities of SOD and CAT of mice significantly decreased(all P＜0.05).Conclusion Remifentanil may promote hemodynamic stability and memory function improvement in HSR mice by inhibiting TXNIP/NLRP3/Caspase-1 signaling pathway.