高乌甲素术后镇痛对食管癌手术患者血浆β-EP，SP and Serum TNF-α，IFN-γ，IL-2的影响
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摘要
目的：通过检测食管癌患者围术期外周血浆β－内啡肽（β－endorphin, β－EP）、P物质（substance P, SP），血清肿瘤坏死因子-α(tumor necrosis factor,TNF-α) 、γ－干扰素(interferon,IFN－γ) 和白细胞介素－2（interleukin,IL-2）表达的动态变化，观察高乌甲素静脉应用和硬膜外复合局麻药对食管癌患者术后的镇痛效果；分析不同术后镇痛方法对患者免疫功能的影响。
方法：选择ASAⅡ－Ⅲ级，病理诊断明确，术前未经放化疗、近期内无明显感染史，心、肺、肝、肾、内分泌及免疫功能无明显异常的食管癌择期手术患者45例。凡术中或术后给予免疫抑制剂治疗以及有异体输血者均被排除。将患者按照术后镇痛方法的不同随机分为三组（每组15例）：A组为对照组,术后当患者自诉疼痛难忍时每次肌注哌替啶50mg；B组为高乌甲素静脉镇痛组；C组为硬膜外高乌甲素镇痛组。术前30分钟肌注安定0.2mg/kg、阿托品0.01 mg/kg。C组患者于T7-8或T8－9间隙进行硬膜外穿刺，置入硬膜外导管4cm，平卧后注入2％利多卡因4ml，确定导管在硬膜外腔后麻醉诱导。采用静脉滴入芬太尼2－4μg/kg，咪达唑仑0.1-0.3mg/kg,罗库溴铵0.6-0.8mg/kg，肌松良好后经口明
视气管插管，接麻醉机（Drager SA-2，美国）机械控制呼吸。潮气量10-12ml/kg,呼吸频率为10次／分钟，氧流量1－2L／min,吸呼比为1：1.5。术中吸入2％－2.5％异氟醚间断应用维库溴胺维持麻醉，必要时静滴芬太尼50－100μg调节麻醉深度。术中监测收缩压（SBP）、舒张压（DBP）、平均动脉压（MAP）、心率（HR）、血氧饱和度（SpO2）。B组术后连接静脉镇痛泵（WZ-6520-05型），药液为高乌甲素3.5mg/kg，用生理盐水稀释至100ml，注入速度2ml/h，连续48小时镇痛；C组术后连接硬膜外镇痛泵（WZ-6522-05型），药液为高乌甲素16mg加入0.75%布比卡因45mg，用生理盐水稀释至200ml，注入速度5ml/h，连续48小时镇痛。手术结束前30分钟，B、C两组患者均缓慢静注高乌甲素4-6mg。所有患者均于术前、术毕及术后6、24、48小时抽取肘静脉血2ml，测定血浆SP、β－EP活性。抽血同时记录患者的平均动脉压、心率和血氧饱和度，此外，术后6、24、48小时，采用视觉模拟评分法（VAS）对疼痛程度进行评估（无痛为0分，最大疼痛为10分），询问患者对镇痛的总体满意程度，并记录有无恶心、呕吐、呼吸困难、皮肤瘙痒等副作用。再分别于术前、术毕、术后24、48、120小时抽取肘静脉血3ml，测定血清TNF-α、IFN－γ及IL-2 的浓度。
结果： （1）平均动脉压（MAP）、心率（HR）血
氧饱和度（SPO2）的变化
A、B、C三组患者术毕、术后6 h、24h各时间点均
略高于术前，但差异不明显（P>0.05）。三组患者组间差
异不明显。
A组术毕和术后6、24、48hHR明显高于术前，有显著性差异（p<0.05）。B、C两组患者术毕、术后6 、24、48h各时间点与术前及A组相比，均无统计学差异（P>0.05）。
患者术后常规吸氧，SPO2维持在96%-99%，三组相比无统计学差异（P>0.05）。
（2）镇痛效果及副作用发生情况 B、C两组术后6 、24、48h各时间点的VAS评分均明显低于A组，差别具有显著性（p<0.05）。B、C两组间，C组术后6、24、48h各时间点的VAS评分明显低于B组（P<0.05）。术后镇痛的总体满意度结果显示，B、C两组明显优于A组（P<0.01），C组的总体满意度略高于B组，但差异无显著性（P>0.05）。所有患者未发生缺氧和低血压现象以及其它与麻醉和镇痛有关的副作用。
（3）血浆神经肽的变化 A组患者术毕、术后6、24、48h β- EP的含量明显高于术前，具有显著性差异（P<0.01）；B、C两组术毕β- EP明显高于术前（P<0.05），但术后6、24、48h各时间点与术前相比均无明显差异（P>0.05）。B、C两组术后6、24、48h各时间点β- EP含量均明显低于A组，差别具有显著性（P<0.05）,B组略高于C组，但两间差异无显著性（P>0.05）。
A、B、C三组患者术毕SP含量都略低于术前，但无统计学差异（P>0.05）；三组患者术后6、24、48h各时间点与术前、组间比较均无显著性差异（P>0.05）。
（4）细胞因子的变化 A组术后24、48h TNF-α浓
度明显高于术前（P<0.01）;B组和C组术毕及术后24、48h与术前相比差异不明显（P>0.05）。B组和C组术后24、48h明显低于A组（P<0.05，），但两组间差异不明显（P>0.05）。
A、B、C三组术毕及术后各时间点IFN－γ与术前相比差异不明显（P>0.05），组间各时间点均无统计学差异（P>0.05）。
A组术毕、术后24、48h IL-2浓度明显低于术前（P<0.01），术后120h仍低于术前，但差异不明显（P>0.05）;B组和C组术毕明显低于术前（P<0.05），术后24、48h与术前相比无明显差异（P>0.05）。组间A组术后24、48小时明显低于B、C两组（P<0.05），B、C两组间差异不明显（P>0.05）。
结论：1. 高乌甲素作为一种中药制剂，硬膜外和静脉都可应用，但硬膜外复合局麻药镇痛组优于静脉镇痛组。2．手术后血浆β－内啡肽含量明显升高，说明手术创伤能引起强烈的应激反应，本实验有效的术后镇痛能降低其含量，从而缓解应激。3．细胞因子在创伤应激反应中的作用至关重要，高乌甲素术后镇痛?
Objectives: The effects of lappaconitine postoperative analgesia on the plasma β－EP ,SP and serum TNF-α, IFN－γ, IL-2 were studied in 45 patients.
Methods: Forty-five patients, ASA gradeⅡ-Ⅲ,who were scheduled for esophageal carcinoma entered the study. All patients were otherwise healthy without sign of hepatic, renal, endorcrinologic, immunologic, severe cardiac and pulmonary diseases. No radiotherapeutic and chemotherapeutic medications were taken, and no sign of infection was observed within 2 weeks before operation. According to postoperative analgesia methods, 45 patients were randomly divided into 3 groups: A group received on-demand pethidine 50mg; B group received continuous lappaconitine; In group C, postoperative analgesia was produced with epidural lappaconitine + bupivacaine. All patients were premedicated with diazepam 0.2 mg/kg,atropine 0.01 mg/kg or scopolamine 0.3 mg/kg
intramuscularly. Thoracic epidural catheters was placed in the epidural space between T7 and T8 or T8 and T9. A 4ml test dose of 1.5% lidocaine was then administered through the epidural catheter to confirm epidural placement of the catheter. After a successful test dose, anesthesia was induced with IV fentanyl 2-4 μg/kg, imidazoline 0.1-0.3 mg/kg and rocuronium 0.6-0.8 mg/kg. Then the trachea was intubated and the general anesthesia was maintained with 2%-5% isoflurane or vecuronium, further increments of fentanyl 50-100μg as required to keep anesthesia depth. SBP, DBP, MAP, HR, SpO2 were monitered before and during operation. Group B received continuous lappaconitine 3.5 mg/kg for 48 hour intravenously. In group C, postoperative analgesia was produced with epidural lappaconitine 16 mg + 0.75% bupivacaine 45mg for 48 hour. Blood samples were taken form peripheral vein before anesthesia, at the end of surgery and 6，24，48 hour post-operation for determination of plasma β－EP and SP by RAID. Pain was assessed by a visual analog scale at 6, 24，48 hour after surgery and side effects were also recorded. Other samples were taken before anesthesia, at the end of operation at 24, 48, 120 hour post-operation to determine serum TNF-α, IFN-γ, IL-2 by RAID or ELISA.
Results: （1）MAP in group A, B, C increased unsignificantly at the end of surgery, 6,24 hour
post-operation compared to pre-operative level. HR in group A increased significantly at the end of surgery, 6、24,48 hour post-operation compared to pre-operative level and but not higher markedly than that in group B and C.
(2) VAS scale in group B or C was lower markedly than that in group A at 6、24、48 hour after operation. VAS scale in group C was lower markedly than that in group B. Satisfactory pain relief achieved similarly in group B and C, but not in group A.
(3) β- EP level increased significantly at the end of surgery compared to pre-operation in each group, but it was lower in group B and C than group A at 6, 24 ,48 hour post-operation. serum SP level remained unsignificant change in three groups.
(4) serum TNF-αin group A increased significantly at 24 ,48 hour post-operation compared to pre-operative level
but not in group B and C, and higher than those in group B and C.
serum IL-2 in group A increased significantly at the end of surgery, 24, 48 hour post-operation compared to pre-operative level. It was lower in group B and C at the end of surgery than that of pre-operation, and lower in group B and C at 24, 48 hour post-operation than that in group A.
serum IFN－γlevel remained unsignificant change in three groups.
Conclusion: 1. As a Chinese medicine, lappaconitine can reduce postoperative pain via epidural ＋bupivacaine or intravenous infusion, but the VAS score between them was different significantly. 2. β－EP levels increased markly after surgery, which indicated that surgical trauma can induce intensive stress response, but effective analgesia can lower its level. 3. Cytokine play an important role in stress response, postoperative pain relief provided by lappaconitine can modulate the release
方法：选择ASAⅡ－Ⅲ级，病理诊断明确，术前未经放化疗、近期内无明显感染史，心、肺、肝、肾、内分泌及免疫功能无明显异常的食管癌择期手术患者45例。凡术中或术后给予免疫抑制剂治疗以及有异体输血者均被排除。将患者按照术后镇痛方法的不同随机分为三组（每组15例）：A组为对照组,术后当患者自诉疼痛难忍时每次肌注哌替啶50mg；B组为高乌甲素静脉镇痛组；C组为硬膜外高乌甲素镇痛组。术前30分钟肌注安定0.2mg/kg、阿托品0.01 mg/kg。C组患者于T7-8或T8－9间隙进行硬膜外穿刺，置入硬膜外导管4cm，平卧后注入2％利多卡因4ml，确定导管在硬膜外腔后麻醉诱导。采用静脉滴入芬太尼2－4μg/kg，咪达唑仑0.1-0.3mg/kg,罗库溴铵0.6-0.8mg/kg，肌松良好后经口明
视气管插管，接麻醉机（Drager SA-2，美国）机械控制呼吸。潮气量10-12ml/kg,呼吸频率为10次／分钟，氧流量1－2L／min,吸呼比为1：1.5。术中吸入2％－2.5％异氟醚间断应用维库溴胺维持麻醉，必要时静滴芬太尼50－100μg调节麻醉深度。术中监测收缩压（SBP）、舒张压（DBP）、平均动脉压（MAP）、心率（HR）、血氧饱和度（SpO2）。B组术后连接静脉镇痛泵（WZ-6520-05型），药液为高乌甲素3.5mg/kg，用生理盐水稀释至100ml，注入速度2ml/h，连续48小时镇痛；C组术后连接硬膜外镇痛泵（WZ-6522-05型），药液为高乌甲素16mg加入0.75%布比卡因45mg，用生理盐水稀释至200ml，注入速度5ml/h，连续48小时镇痛。手术结束前30分钟，B、C两组患者均缓慢静注高乌甲素4-6mg。所有患者均于术前、术毕及术后6、24、48小时抽取肘静脉血2ml，测定血浆SP、β－EP活性。抽血同时记录患者的平均动脉压、心率和血氧饱和度，此外，术后6、24、48小时，采用视觉模拟评分法（VAS）对疼痛程度进行评估（无痛为0分，最大疼痛为10分），询问患者对镇痛的总体满意程度，并记录有无恶心、呕吐、呼吸困难、皮肤瘙痒等副作用。再分别于术前、术毕、术后24、48、120小时抽取肘静脉血3ml，测定血清TNF-α、IFN－γ及IL-2 的浓度。
结果： （1）平均动脉压（MAP）、心率（HR）血
氧饱和度（SPO2）的变化
A、B、C三组患者术毕、术后6 h、24h各时间点均
略高于术前，但差异不明显（P>0.05）。三组患者组间差
异不明显。
A组术毕和术后6、24、48hHR明显高于术前，有显著性差异（p<0.05）。B、C两组患者术毕、术后6 、24、48h各时间点与术前及A组相比，均无统计学差异（P>0.05）。
患者术后常规吸氧，SPO2维持在96%-99%，三组相比无统计学差异（P>0.05）。
（2）镇痛效果及副作用发生情况 B、C两组术后6 、24、48h各时间点的VAS评分均明显低于A组，差别具有显著性（p<0.05）。B、C两组间，C组术后6、24、48h各时间点的VAS评分明显低于B组（P<0.05）。术后镇痛的总体满意度结果显示，B、C两组明显优于A组（P<0.01），C组的总体满意度略高于B组，但差异无显著性（P>0.05）。所有患者未发生缺氧和低血压现象以及其它与麻醉和镇痛有关的副作用。
（3）血浆神经肽的变化 A组患者术毕、术后6、24、48h β- EP的含量明显高于术前，具有显著性差异（P<0.01）；B、C两组术毕β- EP明显高于术前（P<0.05），但术后6、24、48h各时间点与术前相比均无明显差异（P>0.05）。B、C两组术后6、24、48h各时间点β- EP含量均明显低于A组，差别具有显著性（P<0.05）,B组略高于C组，但两间差异无显著性（P>0.05）。
A、B、C三组患者术毕SP含量都略低于术前，但无统计学差异（P>0.05）；三组患者术后6、24、48h各时间点与术前、组间比较均无显著性差异（P>0.05）。
（4）细胞因子的变化 A组术后24、48h TNF-α浓
度明显高于术前（P<0.01）;B组和C组术毕及术后24、48h与术前相比差异不明显（P>0.05）。B组和C组术后24、48h明显低于A组（P<0.05，），但两组间差异不明显（P>0.05）。
A、B、C三组术毕及术后各时间点IFN－γ与术前相比差异不明显（P>0.05），组间各时间点均无统计学差异（P>0.05）。
A组术毕、术后24、48h IL-2浓度明显低于术前（P<0.01），术后120h仍低于术前，但差异不明显（P>0.05）;B组和C组术毕明显低于术前（P<0.05），术后24、48h与术前相比无明显差异（P>0.05）。组间A组术后24、48小时明显低于B、C两组（P<0.05），B、C两组间差异不明显（P>0.05）。
结论：1. 高乌甲素作为一种中药制剂，硬膜外和静脉都可应用，但硬膜外复合局麻药镇痛组优于静脉镇痛组。2．手术后血浆β－内啡肽含量明显升高，说明手术创伤能引起强烈的应激反应，本实验有效的术后镇痛能降低其含量，从而缓解应激。3．细胞因子在创伤应激反应中的作用至关重要，高乌甲素术后镇痛?
Objectives: The effects of lappaconitine postoperative analgesia on the plasma β－EP ,SP and serum TNF-α, IFN－γ, IL-2 were studied in 45 patients.
Methods: Forty-five patients, ASA gradeⅡ-Ⅲ,who were scheduled for esophageal carcinoma entered the study. All patients were otherwise healthy without sign of hepatic, renal, endorcrinologic, immunologic, severe cardiac and pulmonary diseases. No radiotherapeutic and chemotherapeutic medications were taken, and no sign of infection was observed within 2 weeks before operation. According to postoperative analgesia methods, 45 patients were randomly divided into 3 groups: A group received on-demand pethidine 50mg; B group received continuous lappaconitine; In group C, postoperative analgesia was produced with epidural lappaconitine + bupivacaine. All patients were premedicated with diazepam 0.2 mg/kg,atropine 0.01 mg/kg or scopolamine 0.3 mg/kg
intramuscularly. Thoracic epidural catheters was placed in the epidural space between T7 and T8 or T8 and T9. A 4ml test dose of 1.5% lidocaine was then administered through the epidural catheter to confirm epidural placement of the catheter. After a successful test dose, anesthesia was induced with IV fentanyl 2-4 μg/kg, imidazoline 0.1-0.3 mg/kg and rocuronium 0.6-0.8 mg/kg. Then the trachea was intubated and the general anesthesia was maintained with 2%-5% isoflurane or vecuronium, further increments of fentanyl 50-100μg as required to keep anesthesia depth. SBP, DBP, MAP, HR, SpO2 were monitered before and during operation. Group B received continuous lappaconitine 3.5 mg/kg for 48 hour intravenously. In group C, postoperative analgesia was produced with epidural lappaconitine 16 mg + 0.75% bupivacaine 45mg for 48 hour. Blood samples were taken form peripheral vein before anesthesia, at the end of surgery and 6，24，48 hour post-operation for determination of plasma β－EP and SP by RAID. Pain was assessed by a visual analog scale at 6, 24，48 hour after surgery and side effects were also recorded. Other samples were taken before anesthesia, at the end of operation at 24, 48, 120 hour post-operation to determine serum TNF-α, IFN-γ, IL-2 by RAID or ELISA.
Results: （1）MAP in group A, B, C increased unsignificantly at the end of surgery, 6,24 hour
post-operation compared to pre-operative level. HR in group A increased significantly at the end of surgery, 6、24,48 hour post-operation compared to pre-operative level and but not higher markedly than that in group B and C.
(2) VAS scale in group B or C was lower markedly than that in group A at 6、24、48 hour after operation. VAS scale in group C was lower markedly than that in group B. Satisfactory pain relief achieved similarly in group B and C, but not in group A.
(3) β- EP level increased significantly at the end of surgery compared to pre-operation in each group, but it was lower in group B and C than group A at 6, 24 ,48 hour post-operation. serum SP level remained unsignificant change in three groups.
(4) serum TNF-αin group A increased significantly at 24 ,48 hour post-operation compared to pre-operative level
but not in group B and C, and higher than those in group B and C.
serum IL-2 in group A increased significantly at the end of surgery, 24, 48 hour post-operation compared to pre-operative level. It was lower in group B and C at the end of surgery than that of pre-operation, and lower in group B and C at 24, 48 hour post-operation than that in group A.
serum IFN－γlevel remained unsignificant change in three groups.
Conclusion: 1. As a Chinese medicine, lappaconitine can reduce postoperative pain via epidural ＋bupivacaine or intravenous infusion, but the VAS score between them was different significantly. 2. β－EP levels increased markly after surgery, which indicated that surgical trauma can induce intensive stress response, but effective analgesia can lower its level. 3. Cytokine play an important role in stress response, postoperative pain relief provided by lappaconitine can modulate the release
引文
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10 Hu D,Chen B,Lin S,et al.Changes in substance P in the jejuna of rats after burns.Burns,1996,22(6):463-467
11 王红兵，金士翱，任忠信.可乐定对脊髓P物质释放的影响.中华麻醉学杂志，1998，18（4）：222－4
12 赵云富，姜晓钟，胡世辉，等.三叉神经痛患者血液P物质及其临床意义.第二军医大学学报，2000，21（1）：81－83
13 M Ono and T Satoh.Pharmacological studies on Lappaconitine:antinociception and inhibition of the spinal action of substance P and somatostatin.Jan.J.Pharmacol,1991;55:523-530
14 McBride WT,Armstrong MA,McBride SJ.Immunomodulation :an important concept in modern anesthesia.Anaesthesia,1996,51:465-473
15 Patel PM,Flemming CL,Russell SJ,et al.Cytokine gene transfer as a therapeutic strategy. J Immunother,1993,14:310
16 Yamada T,Hisanaga M,Nakajima Y,et al.Serum interleukin-6, interleukin-8,hepatocute growth factor,and nitric oxide changes during thoracic surgery.World J Surg,1998,22:783-790
17 Van BH MI,Van SJH,et al.peritoneal cytokine release after elective gastrointestinal surgery and postoperative complications.Am J Surg,1998,175:311-316
18 Kragsbjerg F,Holmbery H,Vikerfors T.Serum concentration of interleukin-6,tumour necrosis factor-α,and C-teactive protein in patients undergoing major operations.Eur J Surg,1995,161:17
19 王宏志，胡永华，宛凤玲，等.手术创伤对胸部肿瘤患者血清白细胞介素2受体、白细胞介素6和肿瘤坏死因子α表达的影响.中国肿瘤临床与康复，2002，9（4）：10－13
龚非力.基础免疫学.第一版.湖北：湖北科学技术出版
20 社.1998，141－143
21 Osuka K, Suzuki Y, Saito K,et al. Changes in serum cytokine concentrations after neurosurgical procedures. Acta Neurochir , 1996,138(8):970-6
22 Heimlich F, Dietz A, Daniel V, et al. Immunosuppression caused by head and neck surgery. HNO, 1999 ,47(10):885-92
23 Pirenne J, Ribbens C, Medot M, et al. Adverse effect of abdominal operations on production of interferon-gamma. Eur J Surg, 1995,161(2):77-83
24 张家骅，冉江华，张捷，等.结直肠癌围手术期T细胞亚群、肿瘤坏死因子－α和可溶性白细胞介素－2受体的表达.中华普通外科杂志，1998，13：207－209
25 田建华，张肖楠，任锡玲，等.胃癌患者可溶性白细胞介素－2受体与肿瘤坏死因子－α水平的临床观察.中华消化内镜杂志,1998,15：224－227
26 Schluter B,Bergmann U,Johtek C,et al.Impairment of specific host defence mechanism in patients with chronic post-traumatic osteomyelitis.J Trauma,1991,31:68
27 Levy EM,McIntosh T,Black PH.Elevation of irculating beta-endorphinin levels with concomitant depression of immune parameters after traumatic injury.J Trauma,1986,3:246
2 Oscar A.Immunomodulation and epidural anesthesia and analgesia.Regional Anesth, 1995,21(6S):24-25
3 MG Chen, QH Wang, and W Lin. Clinical study in epidural injection with lappaconitine compound for post-operative analgesia. Zhongguo Zhong Xi Yi Jie He Za Zhi, Sep 1996, 16(9): 525-8
Kloosterman T, Von Berg BM, Borgstein P, et
4 al.Uniimpaired immune function after laparoscopic cholecysterctomy.Surg,1994,115(4):424-426
5 MG Chen, QH Wang, and YB Lin. Clinical study in epidural injection with lappaconitine for post-operative analgesia. Zhongguo Zhong Xi Yi Jie He Za Zhi, May 1995,15(5): 274-6
6 Pokele M.Effect of opioid-induced analgesia on beta-endorphin,cortisol and glucose responses in neonates with cardiorespiratory problems.Biology of the Neonate,1993,64:360-367
7 Hartwig AC.Peripheral beta-endorphin and pain modulation.Anesth Prog,1991,38:75-78
8 Luger TA,lotti T.Neuropeptides:role in inflammtary skin diseases.J Eur Acad Dermatol Venerol ,1998,10:207-211
9 Dionne RA, Max MB, Gordon SM, et al.The substance P receptor antagonist CP-99,994 reduce acute postoperative pain.Clin Pharmacol Ther 1998 Nov ;64(5):562-8
10 Hu D,Chen B,Lin S,et al.Changes in substance P in the jejuna of rats after burns.Burns,1996,22(6):463-467
11 王红兵，金士翱，任忠信.可乐定对脊髓P物质释放的影响.中华麻醉学杂志，1998，18（4）：222－4
12 赵云富，姜晓钟，胡世辉，等.三叉神经痛患者血液P物质及其临床意义.第二军医大学学报，2000，21（1）：81－83
13 M Ono and T Satoh.Pharmacological studies on Lappaconitine:antinociception and inhibition of the spinal action of substance P and somatostatin.Jan.J.Pharmacol,1991;55:523-530
14 McBride WT,Armstrong MA,McBride SJ.Immunomodulation :an important concept in modern anesthesia.Anaesthesia,1996,51:465-473
15 Patel PM,Flemming CL,Russell SJ,et al.Cytokine gene transfer as a therapeutic strategy. J Immunother,1993,14:310
16 Yamada T,Hisanaga M,Nakajima Y,et al.Serum interleukin-6, interleukin-8,hepatocute growth factor,and nitric oxide changes during thoracic surgery.World J Surg,1998,22:783-790
17 Van BH MI,Van SJH,et al.peritoneal cytokine release after elective gastrointestinal surgery and postoperative complications.Am J Surg,1998,175:311-316
18 Kragsbjerg F,Holmbery H,Vikerfors T.Serum concentration of interleukin-6,tumour necrosis factor-α,and C-teactive protein in patients undergoing major operations.Eur J Surg,1995,161:17
19 王宏志，胡永华，宛凤玲，等.手术创伤对胸部肿瘤患者血清白细胞介素2受体、白细胞介素6和肿瘤坏死因子α表达的影响.中国肿瘤临床与康复，2002，9（4）：10－13
龚非力.基础免疫学.第一版.湖北：湖北科学技术出版
20 社.1998，141－143
21 Osuka K, Suzuki Y, Saito K,et al. Changes in serum cytokine concentrations after neurosurgical procedures. Acta Neurochir , 1996,138(8):970-6
22 Heimlich F, Dietz A, Daniel V, et al. Immunosuppression caused by head and neck surgery. HNO, 1999 ,47(10):885-92
23 Pirenne J, Ribbens C, Medot M, et al. Adverse effect of abdominal operations on production of interferon-gamma. Eur J Surg, 1995,161(2):77-83
24 张家骅，冉江华，张捷，等.结直肠癌围手术期T细胞亚群、肿瘤坏死因子－α和可溶性白细胞介素－2受体的表达.中华普通外科杂志，1998，13：207－209
25 田建华，张肖楠，任锡玲，等.胃癌患者可溶性白细胞介素－2受体与肿瘤坏死因子－α水平的临床观察.中华消化内镜杂志,1998,15：224－227
26 Schluter B,Bergmann U,Johtek C,et al.Impairment of specific host defence mechanism in patients with chronic post-traumatic osteomyelitis.J Trauma,1991,31:68
27 Levy EM,McIntosh T,Black PH.Elevation of irculating beta-endorphinin levels with concomitant depression of immune parameters after traumatic injury.J Trauma,1986,3:246