创伤后T细胞功能受抑与信号转导变化的关系

The suppression of T cell functions and its relationship with the change of signal transduction after trauma

目的研究创伤小鼠Ｔ细胞功能受抑与信号转导变化之间的关系。方法将Ｂａｌｂ／ｃ小鼠６０只，随机分为正常对照、伤后１、２、４、７、１０天共６组（每组１０只）。制备小鼠闭合性创伤模型，以尼龙毛纤维分离脾细胞中的Ｔ细胞，测定Ｔ细胞功能，并探讨其与细胞内信号转导变化之间的关系。结果创伤小鼠活化Ｔ细胞白细胞介素２（ＩＬ２）ｍＲＮＡ及ＩＬ２受体α（ＩＬ２Ｒα）ｍＲＮＡ水平降低，ＩＬ２生成、ＩＬ２Ｒα表达及Ｔ淋巴细胞转化受抑；创伤后活化Ｔ细胞内ｃＡＭＰ含量升高，ｃＧＭＰ含量、Ｃａ２＋浓度及蛋白激酶Ｃ（ＰＫＣ）活性降低，该变化同Ｔ细胞功能受抑密切相关。此外，腺苷酸环化酶（ＡＣ）、蛋白激酶Ａ（ＰＫＡ）活性增加，ｃＡＭＰ依赖的磷酸二酯酶（ｃＡＭＰＰＤＥ）、钙调素（ＣａＭ）、ＣａＭ依赖的蛋白激酶（ＣａＭＰＫ）活性下降。ｃＧＭＰ激活剂—左旋咪唑、ＰＫＡ抑制剂—Ｈ８、Ｃａ２＋导入剂—Ａ２３１８７、ＰＫＣ激活剂—佛波酯（ＴＰＡ），在体外均可不同程度的提高创伤小鼠活化Ｔ细胞的功能。结论创伤后活化Ｔ细胞内环核苷酸及磷脂酰肌醇代谢系统信号转导途径的改变，参与介导了Ｔ细胞功能的受抑过程。

Objective To study the relationship between the suppression of T cell functions and the change of signal transduction in traumatized mice. Methods 60 Balb/c mice were randomized into six groups: normal control, 1st, 2nd, 4th, 7th, 10th day posttrauma (n=10) A murine closed trauma model was used, T cells were separated from splenocytes using nylon column T cell functions were determined and their relationship with intracellular signal transduction was investigated Results Interleukin 2 (IL2) mRNA and IL2 receptor (IL2R) mRNA levels were decreased in activated T cells from traumatized mice, IL2 production, IL2R expression and T lymphocytes transformation were suppressed cAMP contents in activated T cells were increased after trauma while cGMP contents, free calcium (Ca2+) concentration and protein kinase C (PKC) activities were decreased These changes were closely related to the suppression of T cell functions In addition, adenylate cyclase (AC) and protein kinase A (PKA) activities were increased while cAMPdependent phosphodiesterase (cAMPPDE), calmodulin (CaM), CaMdependent protein kinase (CaMPK) activities were decreased Levamisole (a stimulator of cGMP), H8 (an inhibitor of PKA), A23187 (an ionophore of Ca2+) and TPA (an activator of PKC) could in vitro elevate activated T cell functions after trauma in various degrees Conclusions Alteration in the pathway of signal transduction following trauma related to cyclic nucleotide and phosphatidylinositol metabolism in activated T cells participate in mediating the suppressive progress of T cell functions