BCRP-BBB与右美托咪定改善轻度高胆红素血症患者术后认知功能的关系
Relationship between BCRP-BBB and dexmedetomidine-induced improvement in postoperative cog-nitive function in patients with mild hyperbilirubinemia
孙熠 1王海云 1赵茗姝 1李青 1王一珍1
作者信息
- 1. 天津医科大学三中心临床学院 天津市第三中心医院麻醉科 天津市重症疾病体外生命支持重点实验室 天津市人工细胞工程技术研究中心 天津市肝胆疾病研究所,天津 300170
- 折叠
摘要
目的 评价乳腺癌耐药蛋白(BCRP)-血脑屏障(BBB)与右美托咪定改善轻度高胆红素血症患者术后认知功能的关系.方法 本研究为前瞻性研究.选择天津市第三中心医院2022年12月至2023年8月择期行胆囊切除术、胆总管探查取石术和T管引流术的胆总管结石轻度高胆红素血症患者90例,性别不限,年龄55~69岁,BMI 22~28 kg/m2,ASA分级Ⅱ或Ⅲ级,术前简易智力状态检查量表(MMSE)评分≥20分.采用随机数字表法将患者分为2组(n=45):对照组(C组)和右美托咪定组(D组).D组麻醉诱导后经10 min静脉输注右美托咪定负荷剂量0.5 μg/kg,随后以0.6μg·kg-1·h-1的速率静脉输注至术毕;C组给予等容量生理盐水.于术前2d和术后1、3、5、7、14d时采用MMSE和蒙特利尔认知评估量表(MoCA)评估认知功能,采用ELISA法检测血清BCRP浓度、认知功能血清学指标[血清S100β、β淀粉样蛋白42(Aβ42)、MDA浓度]、BBB血清学指标[血清胶质纤维酸性蛋白(GFAP)、血小板反应蛋白1(TSP-1)和闭合蛋白5(claudin-5)浓度].结果 与C组比较,D组MMSE评分和MoCA评分升高,认知功能障碍发生率下降,血清S100β、Aβ42和MDA浓度降低,血清BCRP浓度升高,血清GFAP、claudin-5和TSP-1浓度降低(P<0.05).结论 右美托咪定改善轻度高胆红素血症患者术后认知功能的机制,可能与上调BCRP水平,改善BBB功能有关.
Abstract
Objective To evaluate the relationship between breast cancer resistance protein(BCRP)-blood brain barrier(BBB)and dexmedetomidine-induced improvement in postoperative cognitive function in patients with mild hyperbilirubinemia.Methods This was a prospective study.Ninety patients of both sexes with mild hyperbilirubinemia caused by choledocholithiasis,aged 55-69 yr,with body mass index of 22-28 kg/m2,of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ,with preoperative Mini-Mental State Examination(MMSE)scores ≥20,scheduled for elective cholecystectomy,exploratory choledocholithotomy and T-tube drainage from December 2022 to August 2023 in the Third Cen-tral Hospital of Tianjin,were divided into 2 groups(n=45 each)using a random number table method:control group(C group)and dexmedetomindine group(D group).After induction of anesthesia,dexme-detomidine was intravenously infused at a loading dose of 0.5 μg/kg over 10 min,followed by an infusion of 0.6 μg·kg-1·h-1 until the end of operation in group D,and the equal volume of normal saline was given instead in group C.At 2 days before operation and 1,3,5,7 and 14 days after operation,the cognitive function was assessed using MMSE and Montreal Cognitive Assessment,and the serum BCRP concentration,concentrations of cognitive function serological indicators(serum S100β,β amyloid 42,malondialdehyde),and concentrations of BBB serological indicators(serum glial fibrillary acidic protein,thrombospondin 1,claudin 5)were determined using enzyme-linked immunosorbent assay.Results Compared with group C,MMSE and Montreal Cognitive Assessment scores were significantly increased,the incidence of cognitive im-pairment was decreased,the serum concentrations of S100β,β amyloid 42 and malondialdehyde were de-creased,the serum concentrations of BCRP were increased,and the serum concentrations of glial fibrillary acidic protein,claudin-5 and thrombospondin 1 were decreased in group D(P<0.05).Conclusions The mechanism by which dexmedetomidine improves postoperative cognitive function may be related to up-regula-ting BCRP levels and improving BBB function in patients with mild hyperbilirubinemia.
关键词
右美托咪啶/ATP结合盒转运体,亚家族G,成员2/血脑屏障/术后认知并发症/高胆红素血症/胆结石Key words
Dexmedetomidine/ATP binding cassette transporter,subfamily G,member 2/Blood-brain barrier/Postoperative cognitive complications/Hyperbilirubinemia/Cholelithiasis引用本文复制引用
基金项目
天津市卫生健康科技面上项目(TJWJ2023MS017)
白求恩公益基金天津麻醉科研发展计划(TJMZ2022-001)
天津市医学重点学科(专科)建设项目(TJYXZDXK-072C)
出版年
2024