结直肠癌病人围术期神经认知障碍危险因素分析及其与血清S100β蛋白、MMP-9及ADP关系

    Analysis of the risk factors of perioperative neurocognitive impairment in patients with colorectal cancer and its relationship with serum S100β protein, MMP-9 and ADP

    • 摘要:
      目的: 分析结直肠癌病人发生围术期神经认知障碍(PND)的危险因素,并探讨血清S100β、MMP-9及ADP水平对PND的预测价值。
      方法: 选择择期行结直肠癌手术的病人89例作为研究对象,根据病人术后简易智力状态检查量表评分分为非PND组和PND组,比较2组病人的年龄、性别、体质量指数、受教育程度、术前平均动脉压、ASA分级、合并疾病(高血压、糖尿病、心肌梗死、脑梗死)、ASA分级、认知功能障碍评分,术中麻醉药物用量、手术时间、麻醉时间、术中输液量、出血量、术后24 h疼痛视觉模拟评分(VAS);术前、术后1 d、术后7 d 收集血液标本测定S100β、基质金属蛋白酶9(MMP-9)及脂联素(ADP)水平。采用多因素logistic回归分析结直肠癌手术病人PND发生的独立危险因素,ROC曲线与DCA曲线验证模型预测能力,采用Pearson相关分析研究组病人的S-100β蛋白、MMP-9、ADP三者之间的关系及其与MMSE评分之间的关系。
      结果: 89例病人中发生PND26例,发生率为28.89%。单因素分析显示,2组病人受教育程度、性别比、ASA分级、术前MMSE评分、瑞芬太尼用量、 术中胶体液用量、术中失血量、术后拔管时间差异均无统计学意义(P > 0.05);PND组病人年龄≥65岁的比例、体质量指数、术前平均动脉压、糖尿病史占比、右美托咪定用量、手术时间和麻醉时间均高于或长于非PND病人(P < 0.05~ P < 0.01);PND组术后血清S-100β蛋白、MMP-9及ADP及水平较非PND组升高(P < 0.01)。多因素logistic回归分析显示、糖尿病史、术后7 d高血清S-100β蛋白、高MMP-9及低ADP水平是出现认知功能障碍的独立影响因素(P < 0.05);采用ROC曲线和DCA曲线对预测模型的评价显示,模型的准确性(Cox & Snell R2 = 0.636,AUC为0.994)和临床应用价值(Nagelkerke R2 = 0.908)均较高。Pearson相关分析结果显示,S-100β蛋白与MMP-9呈正相关(r = 0.776,P < 0.01)与ADP呈负相关(r = –0.348,P < 0.01),与MMSE评分呈负相关(r = –0.405,P < 0.01)。
      结论: 糖尿病史、术后7 d高血清S-100β蛋白、高MMP-9及低ADP水平是PND发生的独立危险因素,以此构建的结直肠癌病人发生PND的多因素logistic回归预测模型准确性良好,具有较高的临床应用价值。

       

      Abstract:
      Objective To analyze the risk factors of perioperative neurocognitive disorders (PND) in colorectal cancer patients, and explore the predictive value of serum S100β, MMP-9, and ADP for PND.
      Methods Eighty-nine patients treated with elective colorectal cancer surgery were selected as research subjects. According to the postoperative Mini-Mental State Examination score, the patients were divided into the non-PND group and PND group. The age, gender, body mass index, education level, preoperative mean arterial pressure, ASA classification, comorbidities (hypertension, diabetes, myocardial infarction, cerebral infarction), anesthesia drug dosage during surgery, operation time, anesthesia time, intraoperative fluid infusion volume, blood loss, and postoperative 24-hour pain visual analog scale (VAS) scores were compared between two groups. The serum levels of S100β, matrix metalloproteinase 9 (MMP-9), and adiponectin (ADP) were detected before surgery and after 1 and 7 days of surgery. Multivariate logistic regression analysis was used to identify the independent risk factors of PND in colorectal cancer surgery patients. The predictive ability of model was validated using ROC curves and DCA curves. Pearson correlation analysis was conducted to study the relationships among S100β protein, MMP-9, ADP and MMSE scores in two groups.
      Results Among 89 patients, 26 cases developed PND, with an incidence rate of 28.89%. The esultsof Univariate analysis showed that there was no statistical significance in the education level, gender ratio, ASA classification, preoperative MMSE score, remifentanil dosage, intraoperative colloid fluid dosage, intraoperative blood loss and extubation time between two groups (P > 0.05). However, the proportion of patients aged over 65 years, body mass index, preoperative mean arterial pressure, history of diabetes, dexmedetomidine dosage, operation time, and anesthesia time in the PND group were higher or longer than those in non-PND group (P < 0.05 to P < 0.01). The Serum S100β protein, MMP-9 and ADP levels in the PND group were higher than those in non-PND group (P < 0.01). The results of multivariate logistic regression analysis indicated that the history of diabetes, high serum S100β protein, high MMP-9 and low ADP levels after 7 days of surgery were the independent influencing factors of cognitive dysfunction (P < 0.05).The evaluation of prediction model using the ROC curve and DCA curve showed that both the accuracy (Cox & Snell R2 = 0.636, AUC = 0.994) and clinical application value (Nagelkerke R2 = 0.908) of model were relatively high. The results of Pearson correlation analysis showed that the S-100β protein was positively correlated with MMP-9 (r = 0.776, P < 0.01), negatively correlated with ADP (r = –0.348, P < 0.01), and negatively correlated with MMSE score (r = –0.405, P < 0.01).
      Conclusions History of diabetes, and high serum S-100β protein, high MMP-9 and low ADP levels after 7 days of surgery are the independent risk factors for the occurrence of PND. The multivariate logistic regression prediction model for PND in colorectal cancer patients constructed based on this has good accuracy and high clinical application value.

       

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