Objective:To investigate the effect of rapamycin on cognitive function of Operative Cognitive Dysfunction rats induced by anesthesia and explore its possible mechanism.Methods:Wistar rats were intraperitoneally inject...Objective:To investigate the effect of rapamycin on cognitive function of Operative Cognitive Dysfunction rats induced by anesthesia and explore its possible mechanism.Methods:Wistar rats were intraperitoneally injected with 70 mg/kg ketamine for 7 days to establish POCD model after anesthesia.The model rats were randomly divided into model group,rapamycin group,everolimus positive group and 3-methyladenine group.The rats in the model group were intraperitoneally injected with the same amount of normal saline,rapamycin group was intraperitoneally injected with 3.5mg/kg rapamycin,everolimus positive group was intraperitoneally injected with 5.0mg/k everolimus,3-methyladenine group was intraperitoneally injected with 3.5mg/kg rapamycin+2.0mg/kg3-methyladenine for 7 days.Morris water maze was used to measure the retention time,the number of times of platform crossing and the latency time of working memory.Ferritin H,ferritin L,S100β,Beclin 1 were determined by ELISA,and P13K,p-Akt,p-mTOR,4EBP1 were determined by Western blot.Results:In rapamycin group,the retention time and the number of crossing platform were significantly higher than those in the model group(t=6.645,P<0.01;t=5.961,P<0.01),and the latency time of working memory was significantly lower than that in the model group(t=3.799,P<0.01);In rapamycin group,ferritin H,ferritin L,S100βwere significantly lower than that in the model group(t=3.248,P<0.01;t=4.137,P<0.01;t=2.915,P<0.01).3-methyladenine group was significantly lower than rapamycin group in the retention time and the number of times of platform penetration(t=5.138,P<0.01;t=4.437,P<0.01),and the latency time of working memory was significantly higher than rapamycin group(t=2.808,P<0.05);Ferritin H,ferritin L and S100βin 3-methyladenine group were significantly higher than those in pamamycin group(t=2.247,P<0.05;t=3.330,P<0.01;t=2.119,P<0.05).In rapamycin group,P13K and p-Akt protein levels did not change,p-mTOR protein and P-4EBP1 expression was down-regulated,after using 3-methyladenine,P-mTOR protein and P-4EBP1 protein was up-regulated.Conclusions:Rapamycin can improve the cognitive function of POCD rats induced by anesthesia,and its mechanism may be related to the activation of mTOR signaling pathway by rapamycin to promote autophagy.展开更多
目的探讨术前合并不同疾病对老年患者POCD的影响。方法择期行妇科全麻手术,年龄在65岁以上患者386例,术前记录是否合并冠心病、高血压、糖尿病、慢性肾功能不全、肝功能不全等,术前1天和术后第1天应用简易智力状态检查(Mini-Mental Stat...目的探讨术前合并不同疾病对老年患者POCD的影响。方法择期行妇科全麻手术,年龄在65岁以上患者386例,术前记录是否合并冠心病、高血压、糖尿病、慢性肾功能不全、肝功能不全等,术前1天和术后第1天应用简易智力状态检查(Mini-Mental State Examination,MMSE)测试方法评定其认知功能并记录,MMSE评分较术前基础值下降2分认为有认知功能障碍,并据此分为发生POCD组和未发生POCD组。结果发生POCD组中合并冠心病、高血压、糖尿病、慢性肾功能不全患者比例高于未发生POCD组,两组比较差异有统计学意义(p<0.05),但两组合并慢性肝功能不全患者比例未见明显差异(p>0.05)。结论老年患者术前合并冠心病、高血压、糖尿病、慢性肾功能不全,POCD发生率增加,合并慢性肝功能不全两组比例未见明显差异。展开更多
基金Hubei Science and Technology Plan Project 2019(No.:2019cfc836)
文摘Objective:To investigate the effect of rapamycin on cognitive function of Operative Cognitive Dysfunction rats induced by anesthesia and explore its possible mechanism.Methods:Wistar rats were intraperitoneally injected with 70 mg/kg ketamine for 7 days to establish POCD model after anesthesia.The model rats were randomly divided into model group,rapamycin group,everolimus positive group and 3-methyladenine group.The rats in the model group were intraperitoneally injected with the same amount of normal saline,rapamycin group was intraperitoneally injected with 3.5mg/kg rapamycin,everolimus positive group was intraperitoneally injected with 5.0mg/k everolimus,3-methyladenine group was intraperitoneally injected with 3.5mg/kg rapamycin+2.0mg/kg3-methyladenine for 7 days.Morris water maze was used to measure the retention time,the number of times of platform crossing and the latency time of working memory.Ferritin H,ferritin L,S100β,Beclin 1 were determined by ELISA,and P13K,p-Akt,p-mTOR,4EBP1 were determined by Western blot.Results:In rapamycin group,the retention time and the number of crossing platform were significantly higher than those in the model group(t=6.645,P<0.01;t=5.961,P<0.01),and the latency time of working memory was significantly lower than that in the model group(t=3.799,P<0.01);In rapamycin group,ferritin H,ferritin L,S100βwere significantly lower than that in the model group(t=3.248,P<0.01;t=4.137,P<0.01;t=2.915,P<0.01).3-methyladenine group was significantly lower than rapamycin group in the retention time and the number of times of platform penetration(t=5.138,P<0.01;t=4.437,P<0.01),and the latency time of working memory was significantly higher than rapamycin group(t=2.808,P<0.05);Ferritin H,ferritin L and S100βin 3-methyladenine group were significantly higher than those in pamamycin group(t=2.247,P<0.05;t=3.330,P<0.01;t=2.119,P<0.05).In rapamycin group,P13K and p-Akt protein levels did not change,p-mTOR protein and P-4EBP1 expression was down-regulated,after using 3-methyladenine,P-mTOR protein and P-4EBP1 protein was up-regulated.Conclusions:Rapamycin can improve the cognitive function of POCD rats induced by anesthesia,and its mechanism may be related to the activation of mTOR signaling pathway by rapamycin to promote autophagy.
文摘目的探讨术前合并不同疾病对老年患者POCD的影响。方法择期行妇科全麻手术,年龄在65岁以上患者386例,术前记录是否合并冠心病、高血压、糖尿病、慢性肾功能不全、肝功能不全等,术前1天和术后第1天应用简易智力状态检查(Mini-Mental State Examination,MMSE)测试方法评定其认知功能并记录,MMSE评分较术前基础值下降2分认为有认知功能障碍,并据此分为发生POCD组和未发生POCD组。结果发生POCD组中合并冠心病、高血压、糖尿病、慢性肾功能不全患者比例高于未发生POCD组,两组比较差异有统计学意义(p<0.05),但两组合并慢性肝功能不全患者比例未见明显差异(p>0.05)。结论老年患者术前合并冠心病、高血压、糖尿病、慢性肾功能不全,POCD发生率增加,合并慢性肝功能不全两组比例未见明显差异。