右美托咪定对老年患者术后神经认知障碍影响及对miR-218-5p/SNX4信号通路调控作用

Effect of dexmedetomidine on postoperative neurocognitive disorder in elderly patients and its regulation on miR-218-5p/SNX4 signal pathway

目的探讨右美托咪定调控mi R-218-5p/SNX4信号通路对老年患者术后神经认知障碍(PND)影响及可能作用机制。方法选择2020年1月至2021年9月择期全身麻醉下行结直肠癌手术的老年患者80例。根据随机数字表法将患者分为右美组(麻醉诱导后在10 min内予右美托咪定0.5μg·kg^(-1),iv,后以0.3μg·kg^(-1)·h^(-1)维持至手术结束前30 min)和对照组(静脉注射等量生理盐水),每组各40例。记录2组患者的一般资料、术中资料,于术前及术后第1、3、7天早晨抽取患者空腹静脉血,采用q PCR法检测血清mi R-218-5p和SNX4表达水平;使用简易精神状态量表(MMSE)与蒙特利尔认知评估量表(Mo CA)进行认知功能评估,评分>26分诊断为PND,记录2组术后第1、3、7天发生PND情况;双荧光素酶实验验证mi R-218-5p与SNX4之间的直接调控关系,在神经元细胞中沉默mi R-218-5p,q PCR检测SNX4表达水平,MTT检测神经元细胞增殖水平。结果在PND发生率方面,右美组在术后第3天(15.0%vs 32.5%)、第7天(10.0%vs 25.0%)及总体PND发生率(15.0%vs 37.5%)显著降低(P<0.05)。在血清mi R-218-5p表达水平方面,右美组在术后第1、3、7天均高于对照组(P<0.05)。在血清SNX4表达水平方面,右美组在术后第1、3、7天的血清SNX4表达水平均显著降低(P<0.05)。mi R-218-5p与SNX4之间存在直接调控关系。沉默mi R-218-5p的表达后,SNX4的表达水平显著上调(P<0.05),而神经元细胞的增殖能力明显被抑制(P<0.05)。结论使用右美托咪定可降低老年结直肠癌手术患者PND发生率,这可能与调控mi R-218-5p/SNX4信号通路有关。

AIM To investigate the effect and possible mechanism of dexmedetomidine regulating miR-218-5p/SNX4 signal pathway on postoperative neurocognitive disorder(PND)in elderly patients.METHODS From January 2020 to September 2021,80 elderly patients undergoing colorectal cancer surgery under selective general anesthesia were selected.According to the method of random number table,the patients were divided into dexmedetomidine group(exmedetomidine 0.5μg·kg^(-1),iv,0.3μg·kg^(-1)·h^(-1)was administered within 10 min after induction of anesthesia,and then maintained until 30min before the end of surgery)and control group(intravenous infusion of the same amount of normal saline),with 40 patients in each group.The general data and intraoperative data of 2 groups of patients were recorded.Fasting venous blood was drawn from patients before operation and on the 1st,3rd and 7th days after operation.The expression levels of serum miR-218-5p and SNX4 were detected by qPCR.The cognitive function was evaluated with the mini mental state examination(MMSE)and the Montreal cognitive assessment(MoCA).PND was diagnosed with a score of more than 26.PND was recorded on the 1st,3rd and 7th days after operation in 2 groups.The direct regulatory relationship between miR-218-5p and SNX4 was verified by double luciferase assay.The miR-218-5p was silenced in neurons,the expression level of SNX4 was detected by qPCR,and the proliferation level of neurons was detected by MTT.RESULTS In terms of PND incidence,the incidence of PND was significantly reduced in the dexmedetomidine group on the 3rd day(15.0%vs 32.5%),the 7th day(10.0%vs 25%),and the overall incidence of PND(15.0%vs 37.5%)(P<0.05)after surgery.In terms of the expression level of serum miR-218-5p,the expression level of serum miR-218-5p in the dexmedetomidine group was higher than that in the control group on the 1st,3rd,and 7th days after surgery(P<0.05).In terms of the expression level of serum SNX4,the expression level of serum SNX4 in the dexmedetomidine group was significantly lower on the1st,3rd and 7th days after surgery(P<0.05).There was a direct regulatory relationship between miR-218-5p and SNX4.After silencing the expression of miR-218-5p,the expression level of SNX4 was significantly increased(P<0.05),while the proliferation ability of neuronal cells was significantly inhibited(P<0.05).CONCLUSION The use of dexmedetomidine can reduce the incidence of PND in elderly patients undergoing colorectal cancer surgery,which may be associated with the regulation of the miR-218-5p/SNX4 signaling pathway.