不同麻醉和镇痛方法对食管癌手术患者外周血T淋巴细胞亚群及Th细胞分化的影响
|
摘要
研究背景恶性肿瘤患者免疫功能低下，手术创伤、麻醉及术后疼痛等因素均可使免疫功能，尤其是细胞免疫功能进一步降低。围术期患者细胞免疫功能状态对控制术后感染、预防肿瘤扩散等具有重要意义。以往的研究证实选择合适的麻醉和(或)镇痛方法对T淋巴细胞亚群比值的改善有所裨益。但是不同麻醉和镇痛方法对开胸手术患者术中和术后辅助性T淋巴细胞(Th细胞)功能分化的影响如何，目前尚无定论。研究表明，Th细胞的功能分化是机体免疫调节作用中的重要环节之一。Th_1和Th_2细胞是一对重要的调节细胞，分别辅助细胞免疫和体液免疫；同时，Th_1和Th_2细胞又互为抑制细胞。因此，Th_1和Th_2细胞的相互平衡与否直接影响机体的免疫功能，并且与疾病状态密切相关。对于肿瘤或者病原体感染，此时如Th_1细胞活跃，则机体处于抵抗状态，反之则为易感状态。为了更深入地反映手术和麻醉过程中机体细胞免疫功能的状态，需要在检测T淋巴细胞亚群比值的基础上进一步了解Th细胞功能分化的情况。本研究拟针对这一环节进行探讨。
目的观察不同麻醉和镇痛方法下，食管癌开胸手术患者术中和术后外周静脉血T淋巴细胞亚群的变化和辅助性T淋巴细胞功能的分化，并探讨相应的可能机理。
方法60例ASAⅠ～Ⅱ级行择期食管癌开胸手术患者，随机均分为3组：Ⅰ组采用全凭静脉麻醉，术后行患者自控静脉镇痛(TIVA+PCIA)；Ⅱ组采用胸段硬膜外阻滞复合静脉全麻，术后行患者自控静脉镇痛(CEGA+PCIA)；Ⅲ组麻醉方法同Ⅱ组，术后行患者自控硬膜外镇痛(CGEA+PCEA)。分别与于麻醉前(T0)，切皮后2h(T1)，术后4h(T2)，术后24h(T3)，术后48h(T4)抽取三组患者的外周静脉血，用流式细胞检测技术测定CD4~+、CD8~+、CD3~+CD8~-IFN-γ~+及CD3~+CD8~-IL-4~+T细胞百分比，计算CD4~+／CD8~+比值。用CD3~+CD8~-IFN-γ~+、CD3~+CD8~-IL-4~+T细胞分别代表Th_1和Th_2细胞，计算Th_1／Th_2比值。分别于T2、T3、T4时间点采用视觉模拟评分(VAS)判定术后镇痛效果。
结果(1)镇痛效果三组均有良好的术后镇痛效果，但Ⅱ、Ⅲ组T2时点的VAS评分明显低于Ⅰ组(P<0．05)，Ⅲ组T3时点的VAS评分明显低于Ⅰ组和Ⅱ组(P<0．05)(表2)。
(2)GD4~+和CD8~+T淋巴细胞亚群的变化麻醉前各组患者的CD4~+％、CD4~+／CD8~+比值之间无显著性差异(P>0．05)。与麻醉前比较，Ⅰ组T1至T4时点CD4~+％、CD4~+／CD8~+比值明显下降(P<0 05)；Ⅱ组T3和T4时点CD4~+％、CD4~+／CD8~+比值明显下降(P<0．05)；Ⅲ组CD4~+％、CD4~+／CD8~+值在各时点间差异无显著性(P>0．05)。Ⅱ组CD4~+％在T1至T3时点明显高于Ⅰ组(P<0．05)，CD4~+／CD8~+比值在T2时点明显高于Ⅰ组(P<0．05)；Ⅲ组CD4~+％、CD4~+／CD8~+比值在T3、T4时点明显高于Ⅱ组(P<0．05) (表3)。
(3)辅助性T淋巴细胞的变化麻醉前各组患者的Th_1％、Th_2％及Th_1／Th_2比值之间无显著性差异(P>0．05)。与麻醉前比较，各组T2至T4时点Th_1％均明显下降(P<0．05)；Ⅰ、Ⅱ组T2至T4时点Th_2％明显升高(P<0．05)；Ⅲ组T3时点Th_2％明显升高(P<0．05)；Ⅰ组T2至T4时点的Th_1／Th_2比值明显下降(P<0．05)；Ⅱ和Ⅲ组T3、T4时点的Th_1／Th_2比值明显下降(P<0．05)。Ⅱ、Ⅲ组的Th_1／Th_2比值在T2时点明显高于Ⅰ组(P<0．05)；Ⅲ组Th_1／Th_2比值在T3、T4时点均明显高于Ⅱ组(P<0．05)(表3)。
结论食管癌开胸手术患者在术中和术后免疫功能受到抑制，CD4~+T淋巴细胞百分比降低，CD4~+／CD8~+比值下降以及Th_1／Th_2平衡向Th_2偏移。胸段硬膜外阻滞复合全麻辅以术后硬膜外镇痛能够减缓食管癌开胸手术患者术中和术后外周血CD4~+T淋巴细胞百分比和CD4~+／CD8~+比值的下降，并减轻术后Th_0细胞向Th_2细胞的过度分化。因此，对于食管癌开胸手术患者，在麻醉和术后镇痛中辅以硬膜外阻滞将减缓术中和术后细胞免疫抑制的程度。
Objective: To investigate the effects of different anesthesia and analgesia on T lymphocyte subsets and the differentiation of T helper lymphocytes in the esophageal carcinoma patients undergoing thoracic surgery, and to explore the possibility of corresponding mechanism.
Methods: Sixty esophageal carcinoma patients, classified as ASA physical statusⅠ-Ⅱ, scheduled for elective thoracic surgery were randomly divided into three groups with 20 cases each. In groupⅠ, patients received general anesthesia(TIVA) and patient-controlled intravenous analgesia (PCIA) postoperatively; patients in groupⅡreceived general anesthesia combined with thoracic epidural anesthesia (CGEA) during surgery and the same method of analgesia as groupⅠpostoperatively; In groupⅢpatients were anesthetized as well as those in groupⅡ, and received patient-controlled epidural analgesia(PCEA) postoperatively. Venous blood samples were taken before the induction of anesthesia(T0), 2h after incision(T1), 4h after the end of surgery (T2), 24h after the end of surgery (T3) and 48h after the end of surgery (T4). Pain intensity was assessed at T2, T3 and T4 with a box scale (0-10, where 0 is no pain and 10 is the worst pain ever) .The percentage of CD4~+ T lymphocytes(CD4~+), CD8~+ T lymphocytes(CD8~+), IFN-γ-producing T lymphocytes (Th_1) and IL-4-producing T lymphocytes (Th_2) were quantified by using flow cyto-metry. And the ratio of Th_1/Th_2 and CD4~+/CD8~+were calculated. Results: (1) Effects of analgesia The effects of postoperative pain control in all groups were satisfactory. However the VAS scores in groupⅡandⅢwere significantly lower than in groupⅠat T2(P <0.05).And the VAS scores in groupⅢwere significantly lower than in groupⅠandⅡat T3(P<0.05).
(2)Changes of CD4~+ and CD8~+ T lymphocyte subsets The percentage of CD4~+ and the CD4~+/CD8~+ ratios were similar before anesthesia among three groups. Compared with the values at T0, the percentage of CD4~+ from T1 to T4 in groupⅠdecreased significantly, as well as the CD4~+/CD8~+ ratios at T2 and T4 (P <0.05). The percentage of CD4~+ and the CD4~+/CD8~+ ratios in groupⅡdecreased significantly at T3 and T4 (P <0.05). However, the percentage of CD4~+ and the CD4~+/CD8~+ ratios did not change over the period of the study in groupⅢ. The percentage of CD4~+ in groupⅡfrom T1 to T3 were significantly higher than those in groupⅠ(P <0.05). Although the CD4~+/CD8~+ ratios in groupⅡincreased significantly at T2 than that in groupⅠ(P <0.05), there were no significant differences between groupⅠand groupⅡat any other postoperative time points (P> 0.05). The percentage of CD4~+ and the CD4~+/CD8~+ ratios in groupⅢwere significantly higher than those of groupⅡat T3 and T4 (P <0.05).
(3)Changes of T helper lymphocytes(Th) The percentage of Th_1 and Th_2, the ratio of Th_1/Th_2 had no significant difference among three groups(P>0.05). The percentage of Th_1 in all groups from T2 to T4 decreased significantly (P<0.05). The ratio of Th_1/Th_2in groupⅠat T2 and T4, and that in groupⅡat T3 and T4 decreased significantly (P<0.05). The percentage of Th_2 in groupⅠand groupⅡfrom T2 to T4 were increased as well as that in groupⅢat T3(P<0.05). The ratio of Th_1/Th_2in groupⅡandⅢwere higher than that in groupⅠat T2 (P<0.05). The ratio of Th_1/Th_2 in groupⅢwere higher than those in groupⅡat T3 and T4(P<0.05).
Conclusion: The immune function of patients with esophageal cancer after thoracic surgery has been further inhibited, such as CD4~+ T lymphocytes in the lower percentage, decrease of the CD4~+/CD8~+ ratios or the balance of Th_1 and Th_2 felling to the Th_2 shift. These results suggested that general anesthesia combined with thoracic epidural anesthesia and PCEA may preserve the percentage of CD4~+ T lymphocytes and the CD4~+/CD8~+ ratios in peripheral blood after operation, as well as inhibit the differentiation of precursor T helper cells (Th_0) into Th_2. Our data demonstrated that in the esophageal carcinoma patients undergoing thoracic surgery, general anesthesia combined with thoracic epidural anesthesia and PCEA is able to improve the cellular immune function.
目的观察不同麻醉和镇痛方法下，食管癌开胸手术患者术中和术后外周静脉血T淋巴细胞亚群的变化和辅助性T淋巴细胞功能的分化，并探讨相应的可能机理。
方法60例ASAⅠ～Ⅱ级行择期食管癌开胸手术患者，随机均分为3组：Ⅰ组采用全凭静脉麻醉，术后行患者自控静脉镇痛(TIVA+PCIA)；Ⅱ组采用胸段硬膜外阻滞复合静脉全麻，术后行患者自控静脉镇痛(CEGA+PCIA)；Ⅲ组麻醉方法同Ⅱ组，术后行患者自控硬膜外镇痛(CGEA+PCEA)。分别与于麻醉前(T0)，切皮后2h(T1)，术后4h(T2)，术后24h(T3)，术后48h(T4)抽取三组患者的外周静脉血，用流式细胞检测技术测定CD4~+、CD8~+、CD3~+CD8~-IFN-γ~+及CD3~+CD8~-IL-4~+T细胞百分比，计算CD4~+／CD8~+比值。用CD3~+CD8~-IFN-γ~+、CD3~+CD8~-IL-4~+T细胞分别代表Th_1和Th_2细胞，计算Th_1／Th_2比值。分别于T2、T3、T4时间点采用视觉模拟评分(VAS)判定术后镇痛效果。
结果(1)镇痛效果三组均有良好的术后镇痛效果，但Ⅱ、Ⅲ组T2时点的VAS评分明显低于Ⅰ组(P<0．05)，Ⅲ组T3时点的VAS评分明显低于Ⅰ组和Ⅱ组(P<0．05)(表2)。
(2)GD4~+和CD8~+T淋巴细胞亚群的变化麻醉前各组患者的CD4~+％、CD4~+／CD8~+比值之间无显著性差异(P>0．05)。与麻醉前比较，Ⅰ组T1至T4时点CD4~+％、CD4~+／CD8~+比值明显下降(P<0 05)；Ⅱ组T3和T4时点CD4~+％、CD4~+／CD8~+比值明显下降(P<0．05)；Ⅲ组CD4~+％、CD4~+／CD8~+值在各时点间差异无显著性(P>0．05)。Ⅱ组CD4~+％在T1至T3时点明显高于Ⅰ组(P<0．05)，CD4~+／CD8~+比值在T2时点明显高于Ⅰ组(P<0．05)；Ⅲ组CD4~+％、CD4~+／CD8~+比值在T3、T4时点明显高于Ⅱ组(P<0．05) (表3)。
(3)辅助性T淋巴细胞的变化麻醉前各组患者的Th_1％、Th_2％及Th_1／Th_2比值之间无显著性差异(P>0．05)。与麻醉前比较，各组T2至T4时点Th_1％均明显下降(P<0．05)；Ⅰ、Ⅱ组T2至T4时点Th_2％明显升高(P<0．05)；Ⅲ组T3时点Th_2％明显升高(P<0．05)；Ⅰ组T2至T4时点的Th_1／Th_2比值明显下降(P<0．05)；Ⅱ和Ⅲ组T3、T4时点的Th_1／Th_2比值明显下降(P<0．05)。Ⅱ、Ⅲ组的Th_1／Th_2比值在T2时点明显高于Ⅰ组(P<0．05)；Ⅲ组Th_1／Th_2比值在T3、T4时点均明显高于Ⅱ组(P<0．05)(表3)。
结论食管癌开胸手术患者在术中和术后免疫功能受到抑制，CD4~+T淋巴细胞百分比降低，CD4~+／CD8~+比值下降以及Th_1／Th_2平衡向Th_2偏移。胸段硬膜外阻滞复合全麻辅以术后硬膜外镇痛能够减缓食管癌开胸手术患者术中和术后外周血CD4~+T淋巴细胞百分比和CD4~+／CD8~+比值的下降，并减轻术后Th_0细胞向Th_2细胞的过度分化。因此，对于食管癌开胸手术患者，在麻醉和术后镇痛中辅以硬膜外阻滞将减缓术中和术后细胞免疫抑制的程度。
Objective: To investigate the effects of different anesthesia and analgesia on T lymphocyte subsets and the differentiation of T helper lymphocytes in the esophageal carcinoma patients undergoing thoracic surgery, and to explore the possibility of corresponding mechanism.
Methods: Sixty esophageal carcinoma patients, classified as ASA physical statusⅠ-Ⅱ, scheduled for elective thoracic surgery were randomly divided into three groups with 20 cases each. In groupⅠ, patients received general anesthesia(TIVA) and patient-controlled intravenous analgesia (PCIA) postoperatively; patients in groupⅡreceived general anesthesia combined with thoracic epidural anesthesia (CGEA) during surgery and the same method of analgesia as groupⅠpostoperatively; In groupⅢpatients were anesthetized as well as those in groupⅡ, and received patient-controlled epidural analgesia(PCEA) postoperatively. Venous blood samples were taken before the induction of anesthesia(T0), 2h after incision(T1), 4h after the end of surgery (T2), 24h after the end of surgery (T3) and 48h after the end of surgery (T4). Pain intensity was assessed at T2, T3 and T4 with a box scale (0-10, where 0 is no pain and 10 is the worst pain ever) .The percentage of CD4~+ T lymphocytes(CD4~+), CD8~+ T lymphocytes(CD8~+), IFN-γ-producing T lymphocytes (Th_1) and IL-4-producing T lymphocytes (Th_2) were quantified by using flow cyto-metry. And the ratio of Th_1/Th_2 and CD4~+/CD8~+were calculated. Results: (1) Effects of analgesia The effects of postoperative pain control in all groups were satisfactory. However the VAS scores in groupⅡandⅢwere significantly lower than in groupⅠat T2(P <0.05).And the VAS scores in groupⅢwere significantly lower than in groupⅠandⅡat T3(P<0.05).
(2)Changes of CD4~+ and CD8~+ T lymphocyte subsets The percentage of CD4~+ and the CD4~+/CD8~+ ratios were similar before anesthesia among three groups. Compared with the values at T0, the percentage of CD4~+ from T1 to T4 in groupⅠdecreased significantly, as well as the CD4~+/CD8~+ ratios at T2 and T4 (P <0.05). The percentage of CD4~+ and the CD4~+/CD8~+ ratios in groupⅡdecreased significantly at T3 and T4 (P <0.05). However, the percentage of CD4~+ and the CD4~+/CD8~+ ratios did not change over the period of the study in groupⅢ. The percentage of CD4~+ in groupⅡfrom T1 to T3 were significantly higher than those in groupⅠ(P <0.05). Although the CD4~+/CD8~+ ratios in groupⅡincreased significantly at T2 than that in groupⅠ(P <0.05), there were no significant differences between groupⅠand groupⅡat any other postoperative time points (P> 0.05). The percentage of CD4~+ and the CD4~+/CD8~+ ratios in groupⅢwere significantly higher than those of groupⅡat T3 and T4 (P <0.05).
(3)Changes of T helper lymphocytes(Th) The percentage of Th_1 and Th_2, the ratio of Th_1/Th_2 had no significant difference among three groups(P>0.05). The percentage of Th_1 in all groups from T2 to T4 decreased significantly (P<0.05). The ratio of Th_1/Th_2in groupⅠat T2 and T4, and that in groupⅡat T3 and T4 decreased significantly (P<0.05). The percentage of Th_2 in groupⅠand groupⅡfrom T2 to T4 were increased as well as that in groupⅢat T3(P<0.05). The ratio of Th_1/Th_2in groupⅡandⅢwere higher than that in groupⅠat T2 (P<0.05). The ratio of Th_1/Th_2 in groupⅢwere higher than those in groupⅡat T3 and T4(P<0.05).
Conclusion: The immune function of patients with esophageal cancer after thoracic surgery has been further inhibited, such as CD4~+ T lymphocytes in the lower percentage, decrease of the CD4~+/CD8~+ ratios or the balance of Th_1 and Th_2 felling to the Th_2 shift. These results suggested that general anesthesia combined with thoracic epidural anesthesia and PCEA may preserve the percentage of CD4~+ T lymphocytes and the CD4~+/CD8~+ ratios in peripheral blood after operation, as well as inhibit the differentiation of precursor T helper cells (Th_0) into Th_2. Our data demonstrated that in the esophageal carcinoma patients undergoing thoracic surgery, general anesthesia combined with thoracic epidural anesthesia and PCEA is able to improve the cellular immune function.
引文
1 Shimaoka M, Hosotsubo K, Sugimoto M, et al.The influence of surgical stress on T cells:enhancement of early phase lymphocyte activation.Anesth Analg,1998, 87:1431-1435.
2 Ogawa K, Hirai M, Katsube T, et al. Suppression of cellular immunity by surgical stress.Surgery,2000,127:329-336.
3孙来荣，沈宗丽，朱月清，等．不同麻醉与镇痛方法对老龄食管癌患者T细胞亚群 的影响．南京医科大学学报，2006，26(2)：124-127．
4 Z.Y.Wang, C.Q.Wang, J.J.Yang, et al.Which has the least immunity depression during postoperative analgesia-morphine,tramadol,or tramadol with lornoxicam? Clinica Chimica Acta, 2006, 369:40-45.
5周光炎主编．免疫学原理．上海：上海科学技术文献出版社，2000．32．
6 O'Neil-Andersen N J, Lawrence D A.Differential modulation of surface and intracellular protein expression by T cells after stimulation in the presence of monensin or brefeldin A J.Clin Diagn Lab Immunol,2002,9(2):243-250.
7刘莉，张军，方超平，等．流式细胞术检测人和小鼠Th细胞亚群．第三军医大学学 报，2004，10：1845-1848．
8 Salo M. Effects of anaesthesia and surgery on the immune response. Acta Anaesthe-siol Scand, 1992;36:201-220.
9 Ferguson NR,Galley HF, Webster NR. Decreased T helper cell subsets in patientswith severe sepsis. Br J Anaesth. In press.
10 Takagi K, Yamamori H, Morishima Y, et al. Preoperative immunosuppressionits relationship with high morbidity and mortality in patients receiving thoracic eso-phagectomy. Nu-trition, 2001,17:13-17.
11 Lennard TW, Shenton BK, Borzotta A, et al.The influence of surgical operations on components of the human immune system .Br J Surg, 1985, 72: 771-776.
12 Leaver HA, Craig SR, Yap PL, et al .Lymphocyte responses following open and minimally invasive thoracic surgery. Eur J Clin Invest, 2000,30:230-238.
13 Weissman C. The metabolic response to stress: an overview and update. Anesthesiology, 1990,73(2):308-327.
14 Yokoyama M, Itano Y, Katayama H, et al. The Effects of Continuous Epidural Anesthesia and Analgesia on Stress Response and Immune Function in Patients Undergoing Radical Esophagectomy. Anesth Analg, 2005,101:1521-1527.
15 Murayi P, Joris J, Lamy M. General anesthesia vs perimedullaryanesthesia.Rev Med Li ege, 1999,54:588-592.
16 Beilin B, Shavit Y, Trabekin E, et al.The effects of postoperative pain management on immune respone to surgery.Anesth Analg, 2003,97:822-827.
17 Volk T, Schenk M, Voigt M, et al.Postoperative epidural anesthesia preserves lymphocyte, but not monocyte, immune function after major spine surgery.Anesth Analg, 2004, 98:1086-1092.
18 Ben-Eliyahu S. The promotion of tumor metastasis by surgery and stress: Immunological basis and implications for psychoneuroimmunology.Brain Behav Immun,2003,17:S27-S36.
19 Weissman C.The metabolic response to stress: an overview and update. Anesthesiology, 1990,73(2):308-327.
20 Crary B, Hauser SL, Borysenko M, et al.Epinephrine—induced changes in the distribution of lymphocyte subset in peripheral blood of humans. J Immunology, 1983,131: 1178-1181.
21 Kouraklis G, Glinavou A, Raftopoulos L, et al.Epidural analgesia attenuates the systemic stress response to upper abdominal surgery: a randomized trial. Int Surg, 2000, 85(4): 353-357.
22 Qu DM, Jin YF, Ye TH, Cui YS, Li SQ, Zhang ZY.The effects of general anesthesia combined with epidural anesthesia on the stress response in thoracic surgery. Zhonghua Yi Xue Za Zhi, 2003, 83(5):408-411.
23 Li W, Tang HZ, Jiang YB.Influence of different doses of fentanyl on T-lymphocyte subpopulations and natural killer cells of patients with esophageal tumor during preoperation and postoperation. Ai Zheng, 2003 Jun; 22(6):634-636.
24徐明清，黄燕虹，张志．罗哌卡因对外周血CD3、CD4、CD8、CD20、IL-2、 INF-gamma影响的研究．河北医药，2005，11：774-776．
25黄亚辉，钱燕宁．曲马多、吗啡术后自控镇痛对肺癌患者外周血T淋巴细胞亚 群的影响比较．南京医科大学学报，2002，May；22(3)：205-207．
26 Page GG, Blakely WP, Ben-Eliyahu S, et al.Evidence that postoperative pain is a mediator of the tumor-promoting effects of surgery in rats.Pain, 2001,90:191-199.
27 Tjemsland L, S(?)reide JA, Matre R, et al.Pre-operative [correction of Properative] psychological variables predict immunological status in patients with operable breast cancer. Psychooncology, 1997,Dec;6(4):311-320.
28 Wada H, Seki S, Takahashi T.Combined spinal and general anesthesia attenuatesliver metastasis by preserving TH1/TH2 cytokine balance. Anesthesiology, 2007, Mar;106(3):499-506.
29 Pinto RA, Arredondo SM, Bono MR.T helper 1/T helper 2 cytokine imbalance in respiratory syncytial virus infection is associated with increased endogenous plasma cortisol. Pediatrics, 2006, May; 117(5):e878-e886.
30 Sheeran P, Hall GM. Cytokines in anaesthasia [J].Br J Anaesth.l997,78(2): 201-219.
31 Roy S, Balasubramanian S, Sumandeep S, et al .Morphine directs T cells toward T(H2) differentiation. Surgery, 2001,130:304-309.
32金伯泉主编．细胞和分子免疫学实验技术．第四军医大学出版社，2002．84-85．
33 Cras LE, Anna E, Helen F, et al.Spinal but not general anesthesia increases the ration of T helper 1 to helper 2 cell subsets in patients undergoing transurethral resection of the prostate. Anesth Analg, 1998, 87:1421-1425.
34金文杰，钱燕宁，王玲，等．不同浓度曲马多或吗啡预先给药对成人静脉血辅助 性T淋巴细胞分化的影响．中华麻醉学杂志，2005，25：356-359．
35陈平，黄亚辉，金文杰，等．舒芬太尼或氯胺酮预先给药对成人静脉血辅助性T淋 巴细胞分化的影响.中华麻醉学杂志，2006，26：397-400．
36 Roy S, Wang J, Gupta S, et al .Chronic morphine treatment differentiates T helper cells to Th2 effector cells by modulating transcription factors GATA 3 and T-bet.J Neuroimmunol, 2004,147(1-2):78-81.
37 Cruickshank AM, Fraser WD, Burns HJ, et al. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci, 1990,79:1615.
38 Silverman MN, Miller AH, Biron CA, Pearce BD.Characterization of an interleukin-6 and adrenocorticotropin-dependent, immune-to-adrenal pathway during viral infection. Endocrinology, 2004,145:3580-3589.
1 Morkart D, Capo C, Blache JL, et al. Early postoperative compensatory anti-inflammatory response syndrome is associated with septic complications after major surgical trauma in patients with cancer. Br J Surg, 2002,89:1450-1456.
2 Shakhar G, Ben ES. Potential prophylactic measures against postoperative immunosuppression: could they reduce recurrence rates in oncological patients? Ann Surg Oncol, 2003,10:972-992.
3 Vallejo R,Hord ED, Barna SA. Perioperative inmiunosuppressive in cancer patients. J Environ Pathol Toxicol Oncol, 2003,22:139-146.
4 Ben-EKyahu S. The promotion of tumor metastasis by surgery and stress: Immunological basis and impli-cations for psycho-neuroimmunology.Brain Behav Immun, 2003,17:S27-S36.
5 Takagi K, Yamamori H, Morishima Y, et al. Preoperative immunosuppression: its relationship with high morbidity and mortality in patients receiving thoracic esophagectomy. Nutrition, 2001,17:13-17.
6 Leaver HA, Craig SR, Yap PL, et al. Lymphocyte responses following openand minimally invasive thoracic surgery. Eur J Clin Invest, 2000,30:230-238.
7 Pollock RE, Lotzova E, Stanford SD, et al. Effect of surgical stress on murine natural killer cell cytoxicity. J Immunol, 1987,138:171-178.
8 Takabayashi A, Kanai M, Kawai Y, et al.Change in mito-chondrial membrane potential in peripheral blood lymphocytes, especially in natural killer cells, is a possiblemarker for surgical stress on the immune system.World J Surg, 2003,27:659-665.
9 Ogawa K, Hirai M, Katsube T, et al. Suppression of cellular immunity by surgical??stress.Surgery, 2000,127:329-336.
10 Ogata M, Okamoto K, Kohriyama K, et al .Role of interleukin-10 on hyproesponsiveness of endotoxin during surgery.Crit Care Med, 2000,28:3166-3170.
11 Kawasaki T, Ogata M, Kawasaki C, et al .Surgical stress induces endotoxin hyporesponsiveness and an early decrease of monocyte mCD14 and HLA-DR expression during surgery.Anesth Analg, 2001,92 :1322-1326.
12 Tashiro T, Yamamori H, Takagi K, et al. Changes in immune function following surgery for esophageal carcinoma. Nutrition. 1999 Oct;15(10):760-766.
13 Kawasaki T, Kawasaki C, Ogata M, et al.The effect of local anesthetics on monocyte CD 14 and human leukocyte antigen-DR expression. AnesthAnalg, 2004,98:1024-1029.
14 Kiefer RT, Ploppa A ,Krueger, et al.Local anesthetics impair human granulocyte phagocytosis activity, oxidative burst, and CD11b expression in response to staphylococcus aureus. Anesthesiology, 2003,98:842-848.
15 Krog J, Hokland M, A hlburg P, et al.Lipid solubility and concentration dependentattenuation of in vitro natural killer cell cytotoxicity by local anesthetics. Scand, 2002,46:875-878.
16 Larsen B, Hoff G, Wilhelm W, et al.Effect of intravenous anesthetics on spontaneous and endotoxin- stimulated cytokine response in cultured human whole blood. Anesthesiology, 1998,89:1218-1227.
17 陈平，黄亚辉，金文杰，等．舒芬太尼或氯胺酮预先给药对成人静脉血辅助性T 淋巴细胞分化的影响．中华麻醉学杂志，2006，26：397-400．
18 Goto Y, Ho SL, McAdoo J, et al. General versus regional anaesthesia for cataract surgery: effects on neutrophil apoptosis and the postoperative pro-inflammatory state. Eur J Anaesthesiol, 2000,17(8): 474-480.
19 Kotani N, Hashimoto H, Sessler DL, et al. Volatile anesthetics augment expression of proinflammatory cjytokines in rat alveolar macrophages during mechanical ventilation. Anesthesiology, 1999, 91(1): 187-197.
20 Giraud O, Seince PF, Rolland C, et al. Halothane reduces the early??lipopolysaccharide- induced lung inflammation in mechanically ventilated rats. Am J Respir Crit Care Med, 2000,162(6):2278-2286.
21 Gaveriavx RI, Peluso J.Abolition of morphine-Immunosuppression in mice lackingthe mu-opioid receptor gene. Pore Natl Acad Sci USA, 1998,95 :6326-6330.
22 Nelson CJ, Dykstra LA, Lysle DT. Comparison of the time course of Morphine's analgesic and immunologic efects. Anesth Analg, 1997,85:620-626.
23 Sacerdote P, Bainchi M, Gaspani L.The effects of tramadol and morphine on immune responses and pain after surgery in Cancer patients. Anesth Analg, 2000, 90:1411-1413.
24 Yokota T, Uehara K, Nomoto Y.Intrathecal morphine suppresses NK cell activity following abdominal surgery. Can J Anaesth, 2000,47:303-308.
25 Beilin M, Shavit P, Hart M.Effect of anesthesia based on large versus small doses of fentanyl on natural killer cellcytotoxicity in the perioperative period. Anesthe Analg, 1996,82 :496-497.
26金文杰，钱燕宁，王玲，等．不同浓度曲马多或吗啡预先给药对成人静脉血辅助 性T淋巴细胞分化的影响．中华麻醉学杂志，2005，25：356-359．
27 Murayi P, Joris J, Lamy M.General anesthesia vs perimedullaryanesthesia. Rev MedLiege, 1999,54:588-592.
28 Ferguson NR, Gallery HF, Webster NR. T helper cell subset ratios in patients withsevere sepsis. Intensive Care Med, 1999,25:106-109.
29 Cras LE, Anna E, Helen F, et al. Spinal but not general anesthesia increases theration of T helper 1 to helper 2 cell subsets in patients undergoing transurethralresection of the prostate. Anesth Analg, 1998,87:1421 -1425.
30 刘颖涛，李翠荣，唐宏刚，等．针刺复合小剂量硬膜外麻醉对胆囊切除术患者外 周血T淋巴细胞免疫功能的影响．镇刺研究，2001，26：176-177．
31 Schneemilch CE, Bank U. Release of pro- and anti-inflammatory cytokines during different anesthesia procedures. Anaesthesiol Reanim, 2001,26:4-10.
32 Pirtikangas CO, Salo M, Mansikka M, et al.The influence of anaesthetic technique upon the immune response to hysterectomy.A comparison of propofol infusion and isoflurane. Anaesthesia, 1995,50:1056-1061.
33 Beilin B, Shavit Y, Trabekin E, et al.The effects of postoperative pain management on immune respone to surgery. Anesth Analg, 2003,97:822-877.
34 Volk M, Schenk M, Voigt M, et al. Postoperative epidural anesthesia preserves lymphocyte,but not monocyte,immune function after major spine surgery. Anesth Analg, 2004,98:1086-1092.
35魏叔明，陆萍，李继云，等．围术期采用硬膜外镇痛对安氟醚复合麻醉下癌症病 人免疫抑制的影响．中华麻醉学杂志，1999，19：400-402．
36童建成，黄云峰，欧阳静萍．不同配伍布比卡因用于小儿硬膜外术后镇痛对呼吸 SIL-2R、IL的影响．武汉大学学报，2002，23：136-138
37 Gajdosz R. Evaluation of regional analgesia and surgical trauma on seected fators of the human immune system.Folia Med Cracov, 1994,35:69- 86.
2 Ogawa K, Hirai M, Katsube T, et al. Suppression of cellular immunity by surgical stress.Surgery,2000,127:329-336.
3孙来荣，沈宗丽，朱月清，等．不同麻醉与镇痛方法对老龄食管癌患者T细胞亚群 的影响．南京医科大学学报，2006，26(2)：124-127．
4 Z.Y.Wang, C.Q.Wang, J.J.Yang, et al.Which has the least immunity depression during postoperative analgesia-morphine,tramadol,or tramadol with lornoxicam? Clinica Chimica Acta, 2006, 369:40-45.
5周光炎主编．免疫学原理．上海：上海科学技术文献出版社，2000．32．
6 O'Neil-Andersen N J, Lawrence D A.Differential modulation of surface and intracellular protein expression by T cells after stimulation in the presence of monensin or brefeldin A J.Clin Diagn Lab Immunol,2002,9(2):243-250.
7刘莉，张军，方超平，等．流式细胞术检测人和小鼠Th细胞亚群．第三军医大学学 报，2004，10：1845-1848．
8 Salo M. Effects of anaesthesia and surgery on the immune response. Acta Anaesthe-siol Scand, 1992;36:201-220.
9 Ferguson NR,Galley HF, Webster NR. Decreased T helper cell subsets in patientswith severe sepsis. Br J Anaesth. In press.
10 Takagi K, Yamamori H, Morishima Y, et al. Preoperative immunosuppressionits relationship with high morbidity and mortality in patients receiving thoracic eso-phagectomy. Nu-trition, 2001,17:13-17.
11 Lennard TW, Shenton BK, Borzotta A, et al.The influence of surgical operations on components of the human immune system .Br J Surg, 1985, 72: 771-776.
12 Leaver HA, Craig SR, Yap PL, et al .Lymphocyte responses following open and minimally invasive thoracic surgery. Eur J Clin Invest, 2000,30:230-238.
13 Weissman C. The metabolic response to stress: an overview and update. Anesthesiology, 1990,73(2):308-327.
14 Yokoyama M, Itano Y, Katayama H, et al. The Effects of Continuous Epidural Anesthesia and Analgesia on Stress Response and Immune Function in Patients Undergoing Radical Esophagectomy. Anesth Analg, 2005,101:1521-1527.
15 Murayi P, Joris J, Lamy M. General anesthesia vs perimedullaryanesthesia.Rev Med Li ege, 1999,54:588-592.
16 Beilin B, Shavit Y, Trabekin E, et al.The effects of postoperative pain management on immune respone to surgery.Anesth Analg, 2003,97:822-827.
17 Volk T, Schenk M, Voigt M, et al.Postoperative epidural anesthesia preserves lymphocyte, but not monocyte, immune function after major spine surgery.Anesth Analg, 2004, 98:1086-1092.
18 Ben-Eliyahu S. The promotion of tumor metastasis by surgery and stress: Immunological basis and implications for psychoneuroimmunology.Brain Behav Immun,2003,17:S27-S36.
19 Weissman C.The metabolic response to stress: an overview and update. Anesthesiology, 1990,73(2):308-327.
20 Crary B, Hauser SL, Borysenko M, et al.Epinephrine—induced changes in the distribution of lymphocyte subset in peripheral blood of humans. J Immunology, 1983,131: 1178-1181.
21 Kouraklis G, Glinavou A, Raftopoulos L, et al.Epidural analgesia attenuates the systemic stress response to upper abdominal surgery: a randomized trial. Int Surg, 2000, 85(4): 353-357.
22 Qu DM, Jin YF, Ye TH, Cui YS, Li SQ, Zhang ZY.The effects of general anesthesia combined with epidural anesthesia on the stress response in thoracic surgery. Zhonghua Yi Xue Za Zhi, 2003, 83(5):408-411.
23 Li W, Tang HZ, Jiang YB.Influence of different doses of fentanyl on T-lymphocyte subpopulations and natural killer cells of patients with esophageal tumor during preoperation and postoperation. Ai Zheng, 2003 Jun; 22(6):634-636.
24徐明清，黄燕虹，张志．罗哌卡因对外周血CD3、CD4、CD8、CD20、IL-2、 INF-gamma影响的研究．河北医药，2005，11：774-776．
25黄亚辉，钱燕宁．曲马多、吗啡术后自控镇痛对肺癌患者外周血T淋巴细胞亚 群的影响比较．南京医科大学学报，2002，May；22(3)：205-207．
26 Page GG, Blakely WP, Ben-Eliyahu S, et al.Evidence that postoperative pain is a mediator of the tumor-promoting effects of surgery in rats.Pain, 2001,90:191-199.
27 Tjemsland L, S(?)reide JA, Matre R, et al.Pre-operative [correction of Properative] psychological variables predict immunological status in patients with operable breast cancer. Psychooncology, 1997,Dec;6(4):311-320.
28 Wada H, Seki S, Takahashi T.Combined spinal and general anesthesia attenuatesliver metastasis by preserving TH1/TH2 cytokine balance. Anesthesiology, 2007, Mar;106(3):499-506.
29 Pinto RA, Arredondo SM, Bono MR.T helper 1/T helper 2 cytokine imbalance in respiratory syncytial virus infection is associated with increased endogenous plasma cortisol. Pediatrics, 2006, May; 117(5):e878-e886.
30 Sheeran P, Hall GM. Cytokines in anaesthasia [J].Br J Anaesth.l997,78(2): 201-219.
31 Roy S, Balasubramanian S, Sumandeep S, et al .Morphine directs T cells toward T(H2) differentiation. Surgery, 2001,130:304-309.
32金伯泉主编．细胞和分子免疫学实验技术．第四军医大学出版社，2002．84-85．
33 Cras LE, Anna E, Helen F, et al.Spinal but not general anesthesia increases the ration of T helper 1 to helper 2 cell subsets in patients undergoing transurethral resection of the prostate. Anesth Analg, 1998, 87:1421-1425.
34金文杰，钱燕宁，王玲，等．不同浓度曲马多或吗啡预先给药对成人静脉血辅助 性T淋巴细胞分化的影响．中华麻醉学杂志，2005，25：356-359．
35陈平，黄亚辉，金文杰，等．舒芬太尼或氯胺酮预先给药对成人静脉血辅助性T淋 巴细胞分化的影响.中华麻醉学杂志，2006，26：397-400．
36 Roy S, Wang J, Gupta S, et al .Chronic morphine treatment differentiates T helper cells to Th2 effector cells by modulating transcription factors GATA 3 and T-bet.J Neuroimmunol, 2004,147(1-2):78-81.
37 Cruickshank AM, Fraser WD, Burns HJ, et al. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci, 1990,79:1615.
38 Silverman MN, Miller AH, Biron CA, Pearce BD.Characterization of an interleukin-6 and adrenocorticotropin-dependent, immune-to-adrenal pathway during viral infection. Endocrinology, 2004,145:3580-3589.
1 Morkart D, Capo C, Blache JL, et al. Early postoperative compensatory anti-inflammatory response syndrome is associated with septic complications after major surgical trauma in patients with cancer. Br J Surg, 2002,89:1450-1456.
2 Shakhar G, Ben ES. Potential prophylactic measures against postoperative immunosuppression: could they reduce recurrence rates in oncological patients? Ann Surg Oncol, 2003,10:972-992.
3 Vallejo R,Hord ED, Barna SA. Perioperative inmiunosuppressive in cancer patients. J Environ Pathol Toxicol Oncol, 2003,22:139-146.
4 Ben-EKyahu S. The promotion of tumor metastasis by surgery and stress: Immunological basis and impli-cations for psycho-neuroimmunology.Brain Behav Immun, 2003,17:S27-S36.
5 Takagi K, Yamamori H, Morishima Y, et al. Preoperative immunosuppression: its relationship with high morbidity and mortality in patients receiving thoracic esophagectomy. Nutrition, 2001,17:13-17.
6 Leaver HA, Craig SR, Yap PL, et al. Lymphocyte responses following openand minimally invasive thoracic surgery. Eur J Clin Invest, 2000,30:230-238.
7 Pollock RE, Lotzova E, Stanford SD, et al. Effect of surgical stress on murine natural killer cell cytoxicity. J Immunol, 1987,138:171-178.
8 Takabayashi A, Kanai M, Kawai Y, et al.Change in mito-chondrial membrane potential in peripheral blood lymphocytes, especially in natural killer cells, is a possiblemarker for surgical stress on the immune system.World J Surg, 2003,27:659-665.
9 Ogawa K, Hirai M, Katsube T, et al. Suppression of cellular immunity by surgical??stress.Surgery, 2000,127:329-336.
10 Ogata M, Okamoto K, Kohriyama K, et al .Role of interleukin-10 on hyproesponsiveness of endotoxin during surgery.Crit Care Med, 2000,28:3166-3170.
11 Kawasaki T, Ogata M, Kawasaki C, et al .Surgical stress induces endotoxin hyporesponsiveness and an early decrease of monocyte mCD14 and HLA-DR expression during surgery.Anesth Analg, 2001,92 :1322-1326.
12 Tashiro T, Yamamori H, Takagi K, et al. Changes in immune function following surgery for esophageal carcinoma. Nutrition. 1999 Oct;15(10):760-766.
13 Kawasaki T, Kawasaki C, Ogata M, et al.The effect of local anesthetics on monocyte CD 14 and human leukocyte antigen-DR expression. AnesthAnalg, 2004,98:1024-1029.
14 Kiefer RT, Ploppa A ,Krueger, et al.Local anesthetics impair human granulocyte phagocytosis activity, oxidative burst, and CD11b expression in response to staphylococcus aureus. Anesthesiology, 2003,98:842-848.
15 Krog J, Hokland M, A hlburg P, et al.Lipid solubility and concentration dependentattenuation of in vitro natural killer cell cytotoxicity by local anesthetics. Scand, 2002,46:875-878.
16 Larsen B, Hoff G, Wilhelm W, et al.Effect of intravenous anesthetics on spontaneous and endotoxin- stimulated cytokine response in cultured human whole blood. Anesthesiology, 1998,89:1218-1227.
17 陈平，黄亚辉，金文杰，等．舒芬太尼或氯胺酮预先给药对成人静脉血辅助性T 淋巴细胞分化的影响．中华麻醉学杂志，2006，26：397-400．
18 Goto Y, Ho SL, McAdoo J, et al. General versus regional anaesthesia for cataract surgery: effects on neutrophil apoptosis and the postoperative pro-inflammatory state. Eur J Anaesthesiol, 2000,17(8): 474-480.
19 Kotani N, Hashimoto H, Sessler DL, et al. Volatile anesthetics augment expression of proinflammatory cjytokines in rat alveolar macrophages during mechanical ventilation. Anesthesiology, 1999, 91(1): 187-197.
20 Giraud O, Seince PF, Rolland C, et al. Halothane reduces the early??lipopolysaccharide- induced lung inflammation in mechanically ventilated rats. Am J Respir Crit Care Med, 2000,162(6):2278-2286.
21 Gaveriavx RI, Peluso J.Abolition of morphine-Immunosuppression in mice lackingthe mu-opioid receptor gene. Pore Natl Acad Sci USA, 1998,95 :6326-6330.
22 Nelson CJ, Dykstra LA, Lysle DT. Comparison of the time course of Morphine's analgesic and immunologic efects. Anesth Analg, 1997,85:620-626.
23 Sacerdote P, Bainchi M, Gaspani L.The effects of tramadol and morphine on immune responses and pain after surgery in Cancer patients. Anesth Analg, 2000, 90:1411-1413.
24 Yokota T, Uehara K, Nomoto Y.Intrathecal morphine suppresses NK cell activity following abdominal surgery. Can J Anaesth, 2000,47:303-308.
25 Beilin M, Shavit P, Hart M.Effect of anesthesia based on large versus small doses of fentanyl on natural killer cellcytotoxicity in the perioperative period. Anesthe Analg, 1996,82 :496-497.
26金文杰，钱燕宁，王玲，等．不同浓度曲马多或吗啡预先给药对成人静脉血辅助 性T淋巴细胞分化的影响．中华麻醉学杂志，2005，25：356-359．
27 Murayi P, Joris J, Lamy M.General anesthesia vs perimedullaryanesthesia. Rev MedLiege, 1999,54:588-592.
28 Ferguson NR, Gallery HF, Webster NR. T helper cell subset ratios in patients withsevere sepsis. Intensive Care Med, 1999,25:106-109.
29 Cras LE, Anna E, Helen F, et al. Spinal but not general anesthesia increases theration of T helper 1 to helper 2 cell subsets in patients undergoing transurethralresection of the prostate. Anesth Analg, 1998,87:1421 -1425.
30 刘颖涛，李翠荣，唐宏刚，等．针刺复合小剂量硬膜外麻醉对胆囊切除术患者外 周血T淋巴细胞免疫功能的影响．镇刺研究，2001，26：176-177．
31 Schneemilch CE, Bank U. Release of pro- and anti-inflammatory cytokines during different anesthesia procedures. Anaesthesiol Reanim, 2001,26:4-10.
32 Pirtikangas CO, Salo M, Mansikka M, et al.The influence of anaesthetic technique upon the immune response to hysterectomy.A comparison of propofol infusion and isoflurane. Anaesthesia, 1995,50:1056-1061.
33 Beilin B, Shavit Y, Trabekin E, et al.The effects of postoperative pain management on immune respone to surgery. Anesth Analg, 2003,97:822-877.
34 Volk M, Schenk M, Voigt M, et al. Postoperative epidural anesthesia preserves lymphocyte,but not monocyte,immune function after major spine surgery. Anesth Analg, 2004,98:1086-1092.
35魏叔明，陆萍，李继云，等．围术期采用硬膜外镇痛对安氟醚复合麻醉下癌症病 人免疫抑制的影响．中华麻醉学杂志，1999，19：400-402．
36童建成，黄云峰，欧阳静萍．不同配伍布比卡因用于小儿硬膜外术后镇痛对呼吸 SIL-2R、IL的影响．武汉大学学报，2002，23：136-138
37 Gajdosz R. Evaluation of regional analgesia and surgical trauma on seected fators of the human immune system.Folia Med Cracov, 1994,35:69- 86.