时钟节律对肠癌术后胃肠功能的影响及可能的机制

Effect of Circadian Rhythm on Gastrointestinal Function after Colorectal Cancer Surgery and the Possible Mechanism

目的：观察一天中不同时间进行肠道手术对患者术后胃肠功能恢复和炎症反应的影响，并探讨褪黑素在其中的作用。方法选择75例择期开腹行结直肠癌根治术患者，根据手术开始时间分为三组，CT1（8：00～14：00）和CT2组（14：00～20：00）患者各30例，CT3组（20：00～2：00）患者15例，三组患者均选择全凭静脉麻醉。在围术期不同时点抽取患者外周血检测褪黑素、C反应蛋白（CRP）、白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平，同时观察患者术后胃肠道功能恢复情况及术后并发症发生率。结果 CT3组患者麻醉前即刻褪黑素水平比手术即日晨8点明显升高[（23.46±4.13）pg/mL比（16.73±3.77）pg/mL，P0.05]，且明显高于CT1组[（16.30±3.73）pg/mL]及CT2组[（15.75±3.54）pg/mL]麻醉前即刻（P0.05）；CT3组术后肛门排气时间[（73.2±6.3）h]、排便时间[（95.6±8.3）h]、胃液引流量[（452.3±93.7）mL]均明显高于CT1组[（66.7±5.6）h、（8.75±7.4）h、（310.4±78.9）mL]及CT2组[（65.3±6.2）h、（86.7±6.8）h、（307.5±80.1）mL]（P0.05），CT3组术后感染发生率明显高于CT1组及CT2组（53.3%比16.7%、20.0%，P0.05）；CT3组患者术后1、3天的CRP、IL-6、TNF-α水平明显高于CT1组及CT2组[术后1天CRP：（95.6±16.9）mg/L比（78.8±16.4） mg/L、（80.3±15.7）mg/L；IL-6：（124.7±26.9）pg/L比（104.5±24.3）pg/L、（107.5±22.8）pg/L；TNF-α：（379.8±94.6）pg/L比（317.5±83.1）pg/L、（313.2±86.4）pg/L。术后3天CRP：（78.8±15.4）mg/L比（66.3±12.9）mg/L、（67.6±13.5）mg/L；IL-6：（106.3±22.5）pg/L比（92.7±20.4）pg/L、（93.2±21.0）pg/L；TNF-α：（294.3±78.7）pg/L比（244.9±72.0）pg/L、（245.7±71.6）pg/L，P0.05]。结论同一天中不同时间进行肠癌手术会影响手术预后，晚上进行的肠道手术术后炎症反应较强，术后胃肠功能恢复较慢，术后感染发生率较高，其原因可能与褪黑素对时钟节律的调节有关。

Objective To investigate the effect of circadian rhythm on recovery of gastrointestinal function and inflammatory reaction after surgery for colorectal cancer at different time in one day, and to explore the role of melatonin in it. Methods A total of 75 patients undergoing selective surgery for colorectal cancer were enrolled. They were divided into CT1（8：00～14：00） group（n=30）, CT2（14：00～20：00） group（n=30）, and CT3（20：00～2：00） group（n=15） according to the operation time. All patients underwent total intravenous anesthesia. The levels of melatonin, C reactive protein（CRP）, interleukin-6（IL-6）, tumor necrosis factor alpha（TNF-α） in peripheral blood of patients were detected at different perioperative time points. The recovery of gastrointestinal function and the in-cidence of complications were observed after operation. Results Melatonin levels immediately before anesthesia in CT3 group were significantly higher than those at 8：00 of operation day（23.46±4.13pg/mL vs 16.73±3.77pg/mL, P0.05） and those immediately before anesthesia in other two groups（CT1：16.30±3.73pg/mL; CT2：15.75±3.54pg/mL;all P0.05）. Anal exhaust time（73.2±6.3h）, time of defecation（95.6±8.3h）, gastric drainage volume（452.3±93.7mL）of patients in CT3 group were significantly longer or larger than those in other two groups [CT1：66.7±5.6h, 8.75±7.4h, 310.4±78.9mL; CT2：65.3±6.2h, 86.7±6.8h, 307.5±80.1mL; all P0.05]. In CT3 group, the incidence of infec-tion （53.3% vs 16.7%, 20.0%, P0.05） and the levels of CRP, IL-6, TNF-α of patients on postoperative day 1 and day 3 were significantly higher than that in other two group （Day 1 CRP：95.6±16.9mg/L vs 78.8±16.4mg/L, 80.3±15.7mg/L; Day 1 IL-6：124.7±26.9pg/L vs 10.5±24.3pg/L, 107.5±22.8pg/L; Day 1 TNF-α：379.8±94.6pg/L vs 317.5±83.1pg/L, 313.2±86.4pg/L; Day 3 CRP：78.8±15.4mg/L vs 66.3±12.9mg/L, 67.6±13.5mg/L; Day 3 IL-6：106.3±22.5pg/L vs 92.7±20.4pg/L, 93.2±21.0pg/L; Day 3 TNF-α：294.3±78.7pg/L vs 244.9±72.0pg/L, 245.7±71.6pg/L; all P0.05）. Conclusion The operation time of colorectal cancer surgery will affect the prognosis of patients. Under-going the surgery at night will cause stronger inflammation reaction and delay the recovery of gastrointestinal func-tion and have higher incidence of complications. These effect may be related to the regulation of circadian rhythm by melatonin.