Effects of Different Doses of Ulinastatinon Postoperative Cognitive Function and HMGB1 in Elderly Patients
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摘要:
目的 研究不同剂量乌司他丁对老年患者术后认知功能及高迁移族蛋白B1（high mobility group box-1，HMGB1）的影响。 方法 选取2020年05月至2020年9月在昆明医科大学附属甘美医院行择期手术年龄大于60岁的老年患者60例，男36例、女24例，年龄60～84岁，体重46～74 kg，ASA分级Ⅰ～Ⅲ级；根据随机数字表法，将其随机分为实验组（U1、2、3组）和对照组（C组），每组15例。实验组在麻醉诱导前经静脉滴注乌司他丁0.5万U/kg、1万U/kg、1.5万U/kg，对照组给予相同剂量生理盐水静滴。记录患者年龄、学历、住院天数、术后VAS评分等一般情况；收集患者入室后5 min（T1）、出PACU前5 min（T2），术后1 d（T3）、3 d（T4）静脉血，采用双抗体夹心酶联免疫吸附法试验监测患者HMGB1浓度；使用简易智能状态检查量表法评估患者术前（T1）、术后1（T2）、3（T3）、5（T4）、7（T5）d认知功能状况。 结果 HMGB1浓度在各组患者均表现T2、T3、T4时刻较T1时刻升高（P < 0.05），但T4时刻较T3时刻稍有回落（P < 0.05）；术毕时间点，1.5万U/kg的UTI组的HMGB1上升得不如空白组明显（P < 0.05）；术后第1天，1.0万U/kg、1.5万U/kg剂量组HMGB1浓度明显低于对照组（P < 0.05）。各组患者基础MMSE值差异无统计学意义（P > 0.05）。不同剂量UTI组在术后1 d和3 d MMSE评分均呈现下降趋势（P < 0.05），术后5 d、7 d与术后1 d相较差异有统计学意义（P < 0.05）；术后1 d、3 d，对照组MMSE分数明显比1.5万U/kg乌司他丁组低（P < 0.05）。 结论 1.5万U/kg乌司他丁可降低全麻择期腹腔镜手术老年患者POCD的发生，其机制可能与降低循环血中HMGB1相关。 Abstract:Objective To study the effects of different doses of Ulinastatin on postoperative cognitive function and HMBG1 in elderly patients. Methods From May 2020 to September 2020, 60 elderly patients older than 60 years of age were selected for elective surgery in our hospital, 36 males and 24 females, aged 60-84 years, weight 46-74 kg, ASA classification Ⅰ -Level Ⅲ. According to the random number table method, they were randomly divided into experimental group （group U1, 2, 3） and control group （group C）, 15 cases in each group. The experimental group was intravenously infused with ulinastatin 5,000 U/kg, 10,000 U/kg, 15,000 U/kg before anesthesia induction, and the control group was given the same dose of normal saline intravenously. We recorded the patient’ s age, education, length of stay, postoperative VAS score and other general information, and collected the patient’ s venous blood 5 minutes after entering the room （T1）, 5 minutes before leaving the PACU （T2）, 1 day （T3） and 3 days （T4） after the operation. The double antibody sandwich enzyme-linked immunosorbent assay was used to monitor the concentration of HMGB1 in patients; the simple intelligent state check scale method was used to evaluate patients before operation （T1）, postoperative 1 （T2）, 3 （T3）, 5 （T4）, 7 （T5）Day cognitive function status. Results The concentration of HMGB1 in each group of patients was increased at T2, T3, and T4 as compared to T1 （P < 0.05）, but T4 was slightly lower than T3 （P < 0.05）. At the end of the operation, the HMGB1 in the 15,000 U/kg UTI group did not rise significantly as compared to the blank group （P < 0.05）. On the first day after the operation, the HMGB1 concentration in the 10,000 U/kg and 15,000 U/kg dose groups was obvious lower than the control group （P < 0.05）. There was no statistical difference in the basic MMSE value of patients in each group. The MMSE scores of the different doses of UTI group showed a downward trend at 1 and 3 days after surgery （P < 0.05）, and there was a statistically significant difference between 5 and 7 days after surgery and 1 day after surgery （P < 0.05）. On day 1 and day 3, the MMSE score of the control group was significantly lower than that of the 15,000 U/kg Ulinastatin group （P < 0.05）. Conclusion 15,000 U/kg Ulinastatin can reduce the incidence of POCD in elderly patients undergoing elective laparoscopic surgery under general anesthesia, and its mechanism may be related to the reduction of HMGB1 in circulating blood. -
表 1 4组患者一般情况比较[（
$\bar x \pm s$ ）/M（25，75）]Table 1. Comparison of the general conditions among the four groups [（
$\bar x \pm s$ ）/M（25，75）]项目 C组 U1组 U2组 U3组 χ2/F P 例数（n） 15 15 15 15 性别（男/女） 11/4 8/7 9/6 8/7 0.644 0.456 年龄（岁） 69.40 ± 6.80 68.07 ± 5.87 68.87 ± 5.83 68.00 ± 5.18 0.192 0.902 体重（kg） 61.47 ± 6.74 59.33 ± 8.15 58.47 ± 7.60 60.27 ± 8.86 0.391 0.760 学历（小/中/大学） 6/5/4 6/5/4 7/3/5 8/4/3 0.656 0.884 麻醉时间（min） 266.0 ± 86.4 298.3 ± 147.1 313.3 ± 108.6 294.5 ± 102.0 0.457 0.713 手术时间（min） 213.7 ± 115.6 263.0 ± 143.5 286.8 ± 110.4 268.60 ± 103.7 1.031 0.386 输液量（mL） 3490.63
（2335.00，4278.00）*3199.00
（2700.99，4576.14）*4904.12
（3391.67，6578.79）*4668.42
（2871.74，6113.93）8.046 0.045 失血量（mL） 494.44（245.00，675.00） 596.30（445.00，780.43） 559.81（36600，800.40） 427.22（292.39，809.69） 6.086 0.107 尿量（mL） 750.00（598.21，920.37） 972.41（595.45，1392.31） 967.37（684.97，1449.00） 936.84（720.00，1420.00） 5.917 0.116 地氟醚（mL） 104.33 ± 60.47 132.00 ± 66.68 122.40 ± 71.90 127.67 ± 69.59 0.490 0.691 住院天数（d） 16.87 ± 8.06 16.73 ± 3.79 18.40 ± 5.68 16.87 ± 6.02 0.244 0.865 注：与U3组比较，*P < 0.05。 
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表 2 4组患者术后1、2 d VAS评分（
$\bar x \pm s$ ）Table 2. VAS score 1 and 2 days after operation in four groups （
$\bar x \pm s$ ）时间 C组 U1组 U2组 U3组 F P 术后1 d 3.13 ± 0.99 2.93 ± 0.83 3.40 ± 1.06 3.53 ± 0.83 1.264 0.296 术后2 d 2.13 ± 0.83 1.87 ± 0.52 2.13 ± 0.99 2.40 ± 0.99 0.976 0.411
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表 3 4组患者各时间点MMSE分数变化情况[（
$\bar x \pm s$ ），分]Table 3. Changes in MMSE scores of the four groups of patients at each time point [（
$\bar x \pm s$ ），points]组别 MMSE评分 POCD[n（%）] 术前1 d 术后1 d 术后3 d 术后5 d 术后7 d C组 28.40 ± 1.77 24.87 ± 2.67△ 24.73 ± 2.89△ 27.87 ± 2.03▲ 28.60 ± .75▲ 7（46） U1组 28.73 ± 1.58 25.76 ± 3.98△ 26.60 ± 2.80△ 28.00 ± 2.03▲ 28.47 ± 1.41▲ 6（40） U2组 28.67 ± 1.50 26.20 ± 3.23△ 27.87 ± 1.92*△ 28.80 ± 1.47▲ 29.00 ± 1.20▲ 4（26） U3组 28.73 ± 1.44 27.73 ± 1.39*△ 28.40 ± 1.77* 28.73 ± 1.62 29.20 ± 1.21 2（13） 注：与C组比较，*P < 0.05；与T1时刻比较，△P < 0.05；与T2时刻比较，▲P < 0.05。
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表 4 4组患者各时间点HMGB1浓度变化情况[（
$\bar x \pm s$ ），pg/mL]Table 4. Changes of HMGB1 concentration at each time point in the four groups of patients [（
$\bar x \pm s$ ），pg/mL]组别 T1 T2 T3 T4 C组 62.78 ± 19.97 122.93 ± 36.09△ 392.39 ± 112.51△ 206.29 ± 78.46△ U1组 75.76 ± 27.57 118.04 ± 53.58△ 405.95 ± 173.06△ 217.54 ± 133.02△ U2组 74.49 ± 20.78 102.47 ± 37.05△ 258.22 ± 84.62△ 180.02 ± 67.40△ U3组 61.15 ± 13.20 91.63 ± 29.57*△ 235.52 ± 128.87*△ 180.32 ± 98.32△ 注：与C组比较，*P < 0.05；与T1时刻比较，△P < 0.05。
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