Abstract：Objective: To explore the impacts of remimazolam on postoperative cognitive function and neural synapses in elderly rats by regulating protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4)/transcription factor C/EBP-homologous protein (CHOP) pathway. Methods: A cognitive impairment rat model was established by partial liver resection and grouped into a model group, a remimazolam group (6mg/kg), a PERK activator group (5mL/kg MK-28), and a remimazolam+PERK activator group (6mg/kg remimazolam and 5mL/kg MK-28). Rats without liver resection were selected as the control group. The new object recognition experiment and water maze experiment were used to evaluate the cognitive function of each group. Transmission electron microscopy was used to observe the changes in synaptic structure of hippocampal tissue in each group. TUNEL staining was used to observe the apoptosis of hippocampal neurons of rats. Western blot was used to measure the postsynaptic density-95 (PSD95), synaptophysin (SYN), PERK, phosphorylated (p) - ERK, ATF4, and CHOP proteins in the hippocampal tissues of rats. Results: For the control group, the model group had unclear synaptic gaps, severe synaptic damage, decreased platform crossing frequency, total swimming distance, new object recognition index, synaptic number, PSD95 and SYN proteins, but increased escape latency, neuronal apoptosis rate, p-PERK, ATF4, and CHOP proteins (P<0.05). For the model group, the remimazolam group showed obvious improvement in synaptic damage in rats, raised synaptic number, platform crossing frequency, total swimming distance, new object recognition index, PSD95 and SYN proteins, but decreased neuronal apoptosis rate, escape latency, p-PERK, ATF4, and CHOP proteins (P<0.05), however, the PERK activator group showed aggravated synaptic damage, decreased platform crossing frequency, total swimming distance, new object recognition index, synaptic number, PSD95 and SYN proteins, but increased escape latency, neuronal apoptosis rate, p-PERK, ATF4, and CHOP proteins (P<0.05). Intervention with PERK activator on the basis of treatment with remimazolam could reverse the improvement effect of remimazolam on cognitive function in model rats (P<0.05). Conclusion: Remimazolam may improve postoperative cognitive function and neural synapse in elderly rats by inhibiting PERK/ATF4/CHOP pathway.
张艳鹏, 吕洁萍. 瑞马唑仑通过PERK/ATF4/CHOP通路对老年大鼠术后认知功能及神经突触的影响[J]. 河北医学, 2025, 31(10): 1619-1625.
ZHANG Yanpeng, LU Jieping. Impacts of Remimazolam on Postoperative Cognitive Function and Neural Synapses in Elderly Rats Through PERK/ATF4/CHOP Pathway. HeBei Med, 2025, 31(10): 1619-1625.
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2025, Vol. 31 
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