【作者】 金文杰；

【导师】 钱燕宁；

【作者基本信息】 南京医科大学 ， 麻醉学， 2005， 硕士

【副题名】吗啡、芬太尼、曲马多和氯诺昔康对成年人Th0细胞分化的影响及机制

【摘要】 背景:随着生活质量的提高,病人对术后疼痛控制的要求也越来越高。因此术后病人自控镇痛（PCA）在临床广泛应用。PCA可以及时有效地控制术后疼痛,适宜地调节机体的应激反应。大量文献已经报道,某些镇痛药可以抑制机体的免疫系统,尤其是吗啡等阿片类镇痛药物。然而许多镇痛药物尤其是新近使用的镇痛药物对机体免疫的影响尚不得而知,且其分子生物学机制尚不十分清楚。 目的:从Th0细胞分化的角度比较不同镇痛药物对机体细胞免疫功能的影响,从免疫调控角度为选用合适镇痛药物以及适宜浓度提供理论依据,并探讨部分机制。 方法:采集60例健康成年人的外周静脉血,肝素钠抗凝。随机分成四组,每组又分为三个浓度组。Ⅰ组为吗啡组,三个浓度组的最终血药浓度分别为Ⅰa 10ng.ml^-1（M1）,Ⅰb 100ng.ml^-1（M2）,Ⅰc1000ng.ml^-1（M3）;Ⅱ组为芬太尼组,分别为Ⅰa 0.2ng.ml^-1（F1）,Ⅰb更多还原

【Abstract】 Backgroud Failure of cell-mediated immunity is thought to increase the morbidity and mortality rates after trauma and major surgical procedures. One of the reasons associated with this immune dysfunction is the redirection of T cells toward Th2 differentiation. Recently more and more persons pay attention to ache after operation, and patient controlled analgesia(PCA) have widely used. The analgesia agents also play a role in this clinical problem but the mechanisms are not clear. Opioids, especially morphine, can affect immune function, but the effect and mechanisms of lately used new analgesia agents is not clear. Objective To observe the effect of different concentration of morphine, fentanyl, tramadol and lornoxicam on the differentiation of human helper T cells in vitro and study the mechanisms of anesthetics on cell-mediated immunosuppression. Methods Sixty out-patients without immune disease were selected andtheir peripheral blood was collected. Then the whole blood or peripheral blood mononuclear cells (PBMCs) were pretreated with different concentration of morphine, fentanyl, tramadol or lornoxicam for 24 hours, while the control group without any drugs. The level of CD4~+ IFN-γ~+ IL-2~+/ CD4~+IL-4~+IL-10~+ was analyzed by three-color flow cytometry. The intracellular cytokines after stimulation with PMA and Ionomycin were detected by trace whole blood technology. The CD4~+CCR5~+ and CD4~+ CCR3~+ cells in peripheral blood mononuclear cells (PBMCs) were counted to observe the imbalance of Thl/Th2. And the ABC-Elisa method was utilized to measure the levels of IFN-γ、IL-2、IL-4 and IL-10. Results After treatment with morphine, fentanyl, tramadol and lornoxicam, the number of Th2 increased significantly and the ratio of Th1/Th2 decreased dramatically in all groups. At the same time the number of IFN-γ~+IL-2~+ cells decreased and IL-4~+IL-10~+ cells increased sharply as compared with the control group. Compared different concentration in the same analgesia agent, with the concentration elevation, Th2 subsets obviously increased. The levels of cytokines in all drugs changed significantly, IFN-γ and IL-2 decreased, but IL-4 and IL-10 increased.Conclusion Morphine, fentanyl, tramadol and lornoxicam can direct Th0 cells toward Th2 differentiation, especially morphine and fentanyl. The Th2 redirection, as well as the changes in cytokine, showed a dosedependent fashion in all drugs.更多还原