首页|右美托咪定通过上调miR-148a-3p抑制焦亡改善老年大鼠术后认知功能障碍

右美托咪定通过上调miR-148a-3p抑制焦亡改善老年大鼠术后认知功能障碍

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目的 探索右美托咪定对老年大鼠术后认知功能障碍(POCD)的改善作用及其具体机制.方法 18月龄SPF雄性SD大鼠共98只,选取18只作为正常对照组,另80只使用七氟烷+肝叶切除手术建立POCD模型.模型建立成功后,随机分为模型组、模型+生理盐水组、模型+右美组、模型十右美+阿替美唑组,每组20只,探讨右美托咪定对各组老年大鼠POCD的作用.随后,从模型组和模型+右美组中各选取4只,给予miR-148a-3p模拟物或抑制剂,进一步研究右美托咪定改善POCD的机制.结果 七氟烷麻醉+肝叶切除手术导致了大鼠术后认知功能显著下降、神经炎症和焦亡发生增加、海马突触可塑性和miR-148a-3p表达降低(P<0.05);右美托咪定可改善术后认知功能以及上述病理变化(P<0.05);阿替美唑组可显著降低右美改善认知功能的效果(P<0.05);miR-148a-3p模拟物可模拟出右美托咪定对POCD的保护效果,并抑制焦亡,miR-148a-3p抑制剂则可降低右美托咪定的保护效果,并促进焦亡的发生(P<0.05);FMR1可能是miR-148a-3p的下游作用靶点.结论 右美托咪定在能够改善认知功能障碍的同时,还能够改善麻醉手术大鼠海马的突触可塑性、神经炎症,并可能通过上调miR-148a-3p表达抑制焦亡的发生,FMR1可能是miR-148a-3p的下游作用靶点.
Dexmedetomidine improved postoperative cognitive dysfunction(POCD)in elderly rats by up-regulating miR-148a-3p and inhibiting apoptosis
Objective To explore the protective effect of dexmedetomidine on postoperative cognitive dys-function(POCD)in elderly rats and its specific mechanism.Methods 98 male SD rats aged 18 months were selected,with 18 as the normal control group,and the remaining 80 using sevoflurane and liver re-section surgery to establish a POCD model.After the model was established,the rats were randomly di-vided into model group,mode+saline group,model+dexmedetomidine group and model+dexmedeto-midine+atimezole group,with 20 rats in each group to explore the effect of dexmedetomidine on POCD in elderly rats.Then,four rats were selected from each of the model group and model+dexmedetomidine group,and given miR-148a-3p mimics or inhibitors to further study the mechanism of dexmedetomidine in improving POCD.Results Sevoflurane anesthesia+liver lobectomy leaded to a significant decline in post-operative cognitive function,an increase in neuroinflammation and pyroptosis,and a decrease in hippocam-pal synaptic plasticity and miR-148a-3p expression in rats(P<0.05).Dexmedetomidine can improve postoperative cognitive function and the above pathological changes(P<0.05).The effect of dexmedeto-midine on cognitive function was significantly reduced in the model+dexmedetomidine+atimezole group(P<0.05).miR-148a-3p mimic could mimic the protective effect of dexmedetomidine on POCD and in-hibit pyroptosis,while miR-148a-3p inhibitor could reduce the protective effect of dexmedetomidine and promote the occurrence of pyroptosis(P<0.05).FMR1 may be the downstream target of miR-148a-3p.Conclusion Dexmedetomidine can improve cognitive dysfunction,enhance the plasticity of hippocampus in anesthetized rats during surgery,alleviate neuroinflammation,and may inhibit the occurrence of pyropto-sis by up-regulating the expression of miR-148a-3p.FMR1 may be the downstream target of miR-148a-3p.

postoperative cognitive dysfunction(POCD)dexmedetomidinepyroptosismiR-148a-3p

何剑波、秦新刚、李帆、段开明、斯坎带尔·吾守尔、王晓炜

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新疆医科大学第五附属医院麻醉科,乌鲁木齐 830011

中南大学湘雅三医院麻醉科,长沙 410013

术后认知功能障碍 右美托咪定 焦亡 miR-148a-3p

新疆维吾尔自治区自然科学基金项目

2021D01C430

2024

新疆医科大学学报
新疆医科大学

新疆医科大学学报

CSTPCD
影响因子:0.76
ISSN:1009-5551
年,卷(期):2024.47(7)