人参茎叶皂甙提高创伤小鼠T细胞功能的分子机制研究

Molecular Mechanism of Ginsenosides from Stem and Leaf Elevating T cell Functions in Traumatized Mice

目的研究人参茎叶皂甙（ＧＳＬ）提高创伤小鼠Ｔ细胞功能的分子机制。方法利用闭合性创伤小鼠模型，观察ＧＳＬ在体内外对创伤小鼠活化的Ｔ细胞白细胞介素２（ＩＬ－２）、ＩＬ－２受体α链（ＩＬ－２Ｒα）基因转录水平，ｃＡＭＰ、ｃＧＭＰ含量以及磷脂酰肌醇代谢的调节作用。结果ＧＳＬ体内应用（５０ｍｇ·ｋｇ－１·ｄ－１×４ｄ）可明显逆转创伤小鼠活化的Ｔ细胞ＩＬ－２ｍＲＮＡ、ＩＬ－２ＲαｍＲＮＡ、ＩＬ－２及ＩＬ－２Ｒα的受抑状态，降低细胞内ｃＡＭＰ含量，增加ｃＧＭＰ与三磷酸肌醇（ＩＰ３）含量，升高激离钙［Ｃａ２＋］ｉ）浓度、钙调素（ＣａＭ）、ＣａＭ依赖的蛋白激酶（ＣａＭ－ＰＫ）及蛋白激酶Ｃ（ＰＫＣ）的活性。０．１～１００μｇ／ｍｌ的ＧＳＬ在体外可升高创伤小鼠活化的Ｔ细胞ＩＬ－２ｍＲＮＡ及ＩＬ－２ＲαｍＲＮＡ水平，降低ｃＡＭＰ含量，升高ｃＧＭＰ含量、［Ｃａ２＋］ｉ浓度及ＰＫＣ活性。结论ＧＳＬ可通过调节Ｔ细胞内环核苷酸含量及促进磷脂酰肌醇代谢。

Aim To study the molecular mechanism of ginsenosides from stem and leaf (GSL) elevating T cell functions in traumatized mice. Methods On murine closed trauma models, the modulating effect of GSL in vivo and in vitro on interleukin 2 (IL 2), IL 2 receptor α (IL 2Rα) chain gene transcriptional levels, cAMP, cGMP contents, and phosphatidylinositol metabolism in activated T cells from traumatized mice was observed. Results The administration of GSL (50 mg·kg -1 ·d -1 ×4d) in vivo could significantly reverse the suppression of IL 2 mRNA, IL 2Rα mRNA, IL 2 and IL 2Rα levels in activated T cells from traumatized mice, decrease cAMP contents while increasing cGMP and inositol 1,4,5 triphosphate (IP 3) contents, elevating free calcium ([Ca 2+ ]i) concentration and activities of calmodulin (CaM), CaM dependent protein kinase (CaM PK) and protein kinase C (PKC). GSL ranging from 0.1 to 100 μg/ml in vitro could elevate IL 2 mRNA and IL 2Rα mRNA levels in activated T cells from traumatized mice, decrease cAMP contents, increase cGMP contents, [Ca 2+ ]i concentration and PKC activity. Conclusion GSL can enhance IL 2 and IL 2Rα gene transcriptional expression in activated T cells after trauma by modulating cyclic nucleotide contents and improving phosphatidylinositol metabolism.