丙泊酚和异氟醚对乳腺癌患者围术期肿瘤免疫功能的影响

发布时间：2018-07-05 16:52

本文选题：丙泊酚 + 异氟醚　；参考：《上海交通大学》2014年博士论文

【摘要】：目的：乳腺癌是女性最常见的恶性肿瘤。麻醉下手术切除病灶仍是目前治疗实体肿瘤的主要方法，然而围术期免疫抑制的特点，可以造成肿瘤细胞免疫逃逸并发生肿瘤转移。已有研究表明麻醉对免疫系统有调节作用，但关于不同麻醉用药对恶性肿瘤患者围术期细胞免疫功能影响的临床研究甚少。本文旨在探讨丙泊酚及异氟醚麻醉对浸润性乳腺癌患者围术期外周血辅助性T细胞各亚型及其相关细胞因子的影响，为肿瘤患者临床麻醉方法的优选提供依据。方法：选择浸润性乳腺癌患者27例，ASAI~II级，年龄35~75岁，TNM分期I~II级，体重指数30kg/m2，，随机分成三组，丙泊酚全凭静脉麻醉组（静脉组），丙泊酚复合异氟醚麻醉组（静吸组），异氟醚吸入麻醉组（吸入组），每组各9例。患者入室后常规监测无创动脉血压、心电图、脉搏血氧饱和度和Nacrotrend指数。静脉组及静吸组选用咪达唑仑4g/kg，芬太尼2g/kg，丙泊酚1.5~2mg/kg，顺苯磺酸阿曲库铵0.15mg/kg静脉顺序诱导。吸入组用依托米酯0.3mg/kg替代丙泊酚，其余诱导用药同静脉组及静吸组。插管成功后连接麻醉机行机械通气，连续监测并维持呼吸末二氧化碳在35~40mmHg之间。静脉组采用微量泵TCI模式持续输注丙泊酚维持麻醉，靶控浓度3~4g/ml；吸入组持续吸入1.5%~2%浓度的异氟醚；静吸组应用TCI靶控输注丙泊酚1g/ml，全程不变，同时吸入1%~1.5%浓度的异氟醚。术中调整静脉组丙泊酚靶控浓度及吸入组、静吸组异氟醚吸入浓度，维持Nacrotrend指数于D0-2。间断推注芬太尼50~100g和顺苯磺酸阿曲库铵3~4mg，维持患者术中血流动力学稳定及肌肉松弛。三组患者分别于手术当日（D0），术后第一天（D1），术后第七天（D7）采集外周静脉血3ml，流式细胞仪检测外周血中CD4+CD25+Foxp3+调节性T淋巴细胞占CD4+辅助性T淋巴细胞的比例，流式液相多重蛋白定量法检测血浆中细胞因子IL-17A、IFN-γ和IL-10浓度。结果：三组患者在围术期各检测时点外周血CD4+CD25+Foxp3+调节性T淋巴细胞占CD4+辅助性T淋巴细胞的百分比及血浆IFN-γ的浓度未发生显著变化（p0.05）；静脉组患者血浆IL-17A浓度在D1时较D0时明显下降（p0.001)，组间比较，D1时静脉组IL-17A浓度明显低于静吸组和吸入组（p=0.002），至D7时刻，三组IL-17A水平之间差异不明显（p0.05）；吸入组患者血浆IL-10浓度在D1时较D0时显著增高（p=0.01），组间比较，D1时吸入组IL-10浓度显著高于静脉组（p=0.016）和静吸组（p=0.043），至D7时刻，静吸组和吸入组患者的IL-10水平仍明显高于静脉组患者（p=0.027）；相较于D0时，D1时吸入组患者血浆IFN-γ/IL-10比例明显下降（p=0.006），与静脉组比较，吸入组D1时刻IFN-γ/IL-10比值下降更显著（p=0.024），至D7时刻，吸入组此比值仍明显小于静脉组（p=0.007）。结论：1、丙泊酚和异氟醚麻醉对因浸润性乳腺癌行乳房单纯切除加淋巴结清扫术患者外周血CD4+CD25+Foxp3+调节性T细胞的含量没有明显影响。2、麻醉药物能改变机体细胞因子分泌格局，相较于异氟醚，丙泊酚有益于抑制促肿瘤细胞因子IL-17A分泌，抑制IL-10的过度表达，阻止手术后免疫反应由Th1型向Th2型漂移，可能有利于肿瘤患者围术期的免疫保护。
[Abstract]:Objective : Breast cancer is one of the most common malignant tumors in women . surgical resection of the lesions under anesthesia is still the main method for the treatment of solid tumors . However , there is little clinical study on the effect of propofol and isoflurane on the immune function of peripheral blood in patients with malignant tumor .

Methods : Twenty - seven patients with invasive breast cancer , ASAI - II , age 35 - 75 years , TNM stages I ~ II and body weight index of 30kg / m2 were randomly divided into three groups : propofol group ( vein group ) , propofol combined isoflurane anesthesia group ( static suction group ) and isoflurane inhalation anesthesia group ( inhalation group ) .
the inhalation group continuously inhales the isoflurane with the concentration of 1.5 % -2 % ;
The concentrations of CD4 + CD25 + Foxp3 + regulatory T lymphocytes in peripheral blood were measured by flow cytometry . The levels of cytokines IL - 17A , IFN - 纬 and IL - 10 in plasma were measured by flow cytometry .

Results : The percentage of CD4 + CD25 + Foxp3 + regulatory T lymphocytes in CD4 + CD25 + Foxp3 + regulatory T lymphocytes and the concentration of IFN - 纬 in peripheral blood of three groups were not significantly changed ( p < 0.05 ) .
The plasma levels of IL - 17A and IL - 17A were significantly lower ( p = 0.002 ) than those in group D ( p = 0.002 ) , and the level of IL - 17A was not significantly different between the three groups ( p < 0.05 ) .
The levels of IL - 10 were significantly higher at D1 ( p = 0 . 01 ) than those in intravenous group ( p = 0 . 016 ) and group D ( p = 0.043 ) . IL - 10 levels were still significantly higher than those in intravenous group ( p = 0.027 ) .
Compared with vein group , the ratio of IFN - 纬 / IL - 10 decreased significantly ( p = 0 . 024 ) , and the ratio of IFN - 纬 / IL - 10 in the inhalation group was still significantly lower than that in vein group ( p = 0.007 ) .

Conclusion : 1 , propofol and isoflurane anesthesia did not significantly affect the content of CD4 + CD25 + Foxp3 + regulatory T cells in peripheral blood of patients with invasive breast cancer .
【学位授予单位】：上海交通大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R614;R737.9

【参考文献】