【作者】 潘熊熊；

【导师】 钱燕宁；

【作者基本信息】 南京医科大学 ， 麻醉学， 2008， 硕士

【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。Th₁和Th₂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，Th₁和Th₂细胞又互为抑制细胞。因此，Th₁和Th₂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Th₁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Th₁和Th₂细胞，计算Th₁／Th₂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Th₁％、Th₂％及Th₁／Th₂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Th₁％均明显下降（P<0．05）；Ⅰ、Ⅱ组T2至T4时点Th₂％明显升高（P<0．05）；Ⅲ组T3时点Th₂％明显升高（P<0．05）；Ⅰ组T2至T4时点的Th₁／Th₂比值明显下降（P<0．05）；Ⅱ和Ⅲ组T3、T4时点的Th₁／Th₂比值明显下降（P<0．05）。Ⅱ、Ⅲ组的Th₁／Th₂比值在T2时点明显高于Ⅰ组（P<0．05）；Ⅲ组Th₁／Th₂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Th₁／Th₂平衡向Th₂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Th₀细胞向Th₂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。更多还原

【Abstract】 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 （Th₁） and IL-4-producing T lymphocytes （Th₂） were quantified by using flow cyto-metry. And the ratio of Th₁/Th₂ 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 Th₁ and Th₂, the ratio of Th₁/Th₂ had no significant difference among three groups（P>0.05）. The percentage of Th₁ in all groups from T2 to T4 decreased significantly （P<0.05）. The ratio of Th₁/Th₂in groupⅠat T2 and T4, and that in groupⅡat T3 and T4 decreased significantly （P<0.05）. The percentage of Th₂ in groupⅠand groupⅡfrom T2 to T4 were increased as well as that in groupⅢat T3（P<0.05）. The ratio of Th₁/Th₂in groupⅡandⅢwere higher than that in groupⅠat T2 （P<0.05）. The ratio of Th₁/Th₂ 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 Th₁ and Th₂ felling to the Th₂ 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 （Th₀） into Th₂. 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.更多还原