| 摘要: |
| ［摘要］ 目的 探讨乌司他丁对全髋关节置换术（THA）老年患者术后谵妄（POD）的影响及作用机制。方法 招募2022年8月至2023年12月于河南中医药大学第五临床医学院（郑州人民医院）择期行THA的老年患者192例。采用随机数字表法将患者分为乌司他丁组（U组）和生理盐水组（N组），每组96例。U组于麻醉诱导前10 min静脉泵注乌司他丁5 000 U/kg直至手术结束，N组静脉泵注相同体积的生理盐水直至手术结束。术后3 d内采用重症监护病房意识障碍评估法（CAM-ICU）和Richmond躁动-镇静量表（RASS）评估患者POD发生情况。术后48 h采集血样并分离外周血单个核细胞（PBMCs）。应用比色法检测PBMCs中铁离子（Fe2+）浓度、丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性，应用Western blot法测定长链脂酰辅酶A合成酶4（ACSL4）及谷胱甘肽过氧化物酶4（GPX4）表达水平。收集患者的临床资料。结果 U组术前取消手术1例，术后二次手术止血1例，最终纳入94例。N组术后主动退出1例，术后二次手术止血2例，最终纳入93例。术后3 d内U组POD发生率显著低于N组（20.21% vs 35.48%； χ2=5.431，P=0.020）。两组POD严重程度评分及POD持续时间比较差异无统计学意义（P>0.05）。与N组比较，U组术后住院时间显著缩短（P<0.05）。两组手术时间、麻醉总时间、失血量、液体入量及麻醉后监测治疗室（PACU）滞留时间比较差异无统计学意义（P>0.05）。与N组比较，U组术后48 h时PBMCs中Fe2+浓度和MDA含量降低，SOD活性升高，ACSL4蛋白表达量降低，GPX4蛋白表达量升高，差异有统计学意义（P<0.05）。两组不良事件发生率比较差异无统计学意义（P>0.05）。结论 乌司他丁具有神经保护作用，可改善神经功能障碍，降低THA老年患者POD发生率，其作用机制可能与抑制PBMCs中铁死亡和抗氧化应激作用有关。 |
| 关键词: 乌司他丁 术后谵妄 外周血单个核细胞 铁死亡 全髋关节置换术 |
| DOI：10.3969/j.issn.1674-3806.2024.12.10 |
| 分类号: |
| 基金项目:河南省医学科技攻关计划联合共建项目（编号：LHGJ20220799） |
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| A study on the effect and acting mechanism of ulinastatin on postoperative delirium in elderly patients undergoing total hip arthroplasty |
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ZHANG Xungong, WU Xiaoshun
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Department of Anesthesiology, the Fifth Clinical Medical College of Henan University of Chinese Medicine(People′s Hospital of Zhengzhou), Zhengzhou 450000, China
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| Abstract: |
| ［Abstract］ Objective To explore the effect and acting mechanism of ulinastatin on postoperative delirium(POD) in elderly patients undergoing total hip arthroplasty(THA). Methods A total of 192 elderly patients undergoing elective surgery of THA were recruited in the Fifth Clinical Medical College of Henan University of Chinese Medicine(People′s Hospital of Zhengzhou) from August 2022 to December 2023. The patients were divided into ulinastatin group(group U) and normal saline group(group N) by using random number table method, with 96 cases in each group. In group U, 5 000 U/kg of ulinastatin was injected intravenously 10 minutes before anesthesia induction until the end of surgery, and in group N, the same volume of normal saline was injected intravenously until the end of surgery. The patients were assessed for POD by using confusion assessment method-intensive care unit(CAM-ICU) and Richmond Agitation-Sedation Scale(RASS) within 3 days after surgery. Blood samples were collected 48 hours after surgery, and peripheral blood mononuclear cells(PBMCs) were isolated. The concentration of ferric ion(Fe2+), the content of malondialdehyde(MDA) and the activity of superoxide dismutase(SOD) in PBMCs were determined by using the colorimetric method. The expression levels of long-chain acyl-CoA synthetase 4(ACSL4) and glutathione peroxidase 4(GPX4) were determined by using Western blot method. The clinical data of the patients were collected. Results In group U, the operation of 1 patient was canceled before surgery, and 1 patient underwent a second operation to stop bleeding after surgery, and 94 patients were finally included. In group N, 1 patient voluntarily dropped out of the study after surgery, 2 patients underwent a second operation to stop bleeding after surgery, and 93 patients were finally included. Within 3 days after surgery, the incidence of POD in group U was significantly lower than that in group N(20.21% vs 35.48%; χ2=5.431, P=0.020). There were no significant differences in POD severity scores and POD duration between the two groups(P>0.05). Compared with that in group N, the length of postoperative hospitalization in group U was significantly shortened(P<0.05). There were no significant differences in operation time, total anesthesia time, blood loss volume, fluid intake and the duration of stay in postanesthesia care unit(PACU) between the two groups(P>0.05). Compared with group N, group U had a decrease in Fe2+ concentration and MDA content, an increase in SOD activity, a decrease in the expression of ACSL4 protein, and an increase in the expression of GPX4 protein in PBMCs 48 hours after surgery, and the differences were statistically significant(P<0.05). There was no significant difference in the incidence of adverse events between the two groups(P>0.05). Conclusion Ulinastatin has a neuroprotective effect, which can improve neurological dysfunction and reduce the incidence of POD in elderly patients undergoing THA. The mechanism of action may be related to inhibiting ferroptosis in PBMCs and anti-oxidative stress. |
| Key words: Ulinastatin Postoperative delirium(POD) Peripheral blood mononuclear cells(PBMCs) Ferroptosis Total hip arthroplasty |
