帕瑞昔布钠对肺癌患者围术期免疫功能及肿瘤微转移的影响

doi:10.3760/cma.j.cn101202-20220222-00059

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摘要目的探讨帕瑞昔布钠对肺癌患者免疫功能及肿瘤微转移的影响。方法前瞻性随机对照研究。纳入2020年10月—2021年8月蚌埠医学院第一附属医院胸外科择期行胸腔镜肺癌根治术的患者60例,其中男31例、女29例,年龄40~64岁,体质量指数（BMI）20~30 kg/m²,美国麻醉医师协会（ASA）Ⅰ~Ⅱ级,采用随机数字表法分为对照组（30例）和观察组（30例）。观察组患者分别于麻醉诱导前20 min、术后12 h静脉注射40 mg注射用帕瑞昔布钠（5 mL生理盐水稀释）;对照组患者在相同时间点静脉注射生理盐水5 mL。观察并比较2组患者性别、年龄、ASA分级、BMI等基线资料,以及手术时间、术中丙泊酚等麻醉药物用量、术后疼痛视觉模拟评分法（VAS）评分等围术期临床指标。分别于麻醉诱导前20 min（T₀）、手术结束（T₁）、术后24 h（T₂）和术后48 h（T₃）4个时间点采集外周静脉血各5 mL。荧光PCR技术检测人类肺组织特异性基因（LUNX）阳性表达情况,采用流式细胞术测定免疫细胞CD3⁺、CD4⁺、CD8⁺和自然杀伤（NK）细胞水平。结果 2组患者性别、年龄、ASA分级、BMI等基线资料比较,差异均无统计学意义（P值均>0.05）。2组患者手术时间,术中丙泊酚、七氟醚、舒芬太尼、瑞芬太尼和右美托咪定用量,术后疼痛VAS评分比较,差异均无统计学意义（P值均>0.05）。2组患者组内比较,从T₀到T₃CD3⁺、CD4⁺、CD8⁺、NK细胞占比均逐渐降低,组内不同时间点比较差异均有统计学意义（F=1 314.17、737.45、113.87、57.63,P值均<0.05）。T₀时,2组患者CD3⁺、CD4⁺、CD8⁺、NK细胞占比差异均无统计学意义（t=-0.38、-0.93、-0.49、0.91,P值均>0.05）;T₁、T₂、T₃时,对照组CD3⁺、CD4⁺、CD8⁺、NK细胞占比均低于观察组,差异均有统计学意义（T₁时,t=2.47、3.41、2.10、2.11;T₂时,t=2.87、3.67、2.17、2.05;T₃时,t=3.78、3.77、3.58、2.08;P值均<0.05）。2组患者T₀、T₁时LUNX阳性表达率比较,差异无统计学意义（χ²=0.08、0.00,P值均>0.05）;观察组T₂、T₃时LUNX阳性表达率低于对照组,差异有统计学意义（χ²=4.59、7.18,P值均<0.05）。结论围术期应用帕瑞昔布钠对肺癌患者的免疫功能有保护作用,可能会降低患者围术期肿瘤微转移的风险。

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	陈梦婷
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关键词 ：肺肿瘤, 帕瑞昔布钠, 肿瘤微转移, 免疫保护

Abstract：Objective This study aimed to investigate the effects of parecoxib sodium on perioperative immune function and micrometastasis in patients with lung cancer. Methods In this study, a prospective controlled study design was used. Sixty patients undergoing thoracoscopic radical resection of lung cancer, including 31 males and 29 females, who were aged 40-64 years with body mass index (BMI) of 20-30 kg/m² and American Society of Anesthesiologists (ASA) status Ⅰ or Ⅱ, were randomized into two groups: observation group (30 patients) and control group (30 patients). Baseline data, including gender, age, ASA grade, BMI, and perioperative clinical indicators such as operation time, intraoperative dosage of anesthetic drugs, and postoperative pain visual analogue scale (VAS) score, were observed and compared between the two groups. The observation group received intravenous injection of 40 mg of parecoxib sodium 20 min before anesthesia induction and 12 h after surgery, whereas the control group received 5 mL saline injection at the same time points. Five milliliters of venous blood was extracted on the following time points: 20 min before anesthesia induction (T₀), the end of operation (T₁), and 24 h (T₂) and 48 h (T₃) postoperatively. CD3⁺, CD4⁺, and CD8⁺ lymphocyte subsets and NK cell levels in peripheral blood were detected by flow cytometry. The expression of lung-specific X protein (LUNX) was detected by RT-PCR. Results No significant differences in gender, age, ASA grade, BMI, and other baseline data were found between the two groups (all P values > 0.05). In addition, the use of propofol, sevoflurane, sufentanil, remifentanil, dexmedetomidine, postoperative pain VAS scores, and operative time between the two groups showed no significant difference (all P values > 0.05). The proportion of CD3⁺, CD4⁺, CD8⁺, and NK cells decreased gradually at different time points from T₀ to T₃, and the differences within the group in the two groups were significant (F=1 314.17、737.45、113.87、57.63, all P values <0.05). However, the differences in the proportion of CD3⁺, CD4⁺, CD8⁺, and NK cells at T₀ were not significant (t = -0.38, -0.93, -0.49, 0.91; all P values > 0.05). Moreover, the proportions of CD3⁺, CD4⁺, CD8⁺, and NK cells at T₀ were not significant (t = -0.38, -0.93, -0.49, 0.91; all P values > 0.05), and such proportions were lower than those of the control group at T₁, T₂, and T₃ (t=2.47, 3.41, 2.10, 2.11 at T₁; t = 2.87, 3.67, 2.17, 2.05 at T₂; t = 3.78, 3.77, 3.58, 2.08 at T₃: all P values <0.05). No significant difference in LUNX positive expression was found at T₀ and T₁ (χ²=0.078, 0.00; all P values > 0.05), and the LUNX positive expression at T₂ and T₃was lower than that of the control group (χ²=4.59, 7.18; all P values <0.05). Conclusion Parecoxib sodium can improve postoperative immune function in patients with lung cancer, and the use of sodium paroxib may reduce the risk of perioperative tumor micrometastases.

Key words： Lung neoplasms Parecoxib sodium Tumor micrometastasis Immune protection

收稿日期: 2022-02-22

基金资助:安徽省教育厅自然科学重点项目（KJ2017A246、KJ2020A0518）; 蚌埠医学院研究生科研创新计划（Byycxz20042）

通讯作者: 李晓红,Email：lxh552@hotmail.com

引用本文:

陈梦婷, 韩冰, 易铭, 李晓红. 帕瑞昔布钠对肺癌患者围术期免疫功能及肿瘤微转移的影响[J]. 中华解剖与临床杂志, 2022, 27(8): 568-573.
Chen Mengting, Han Bing, Yi Ming, Li Xiaohong. Effects of parecoxib sodium on perioperative immune function and tumor micrometastasis in patients with lung cancer. Chinese Journal of Anatomy and Clinics, 2022, 27(8): 568-573.

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http://www.cjac.com.cn/CN/10.3760/cma.j.cn101202-20220222-00059 或 http://www.cjac.com.cn/CN/Y2022/V27/I8/568

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