18%III度烫伤对小鼠脾脏T淋巴细胞肌醇脂质信号系统及其功能的影响

The influence of 18% TBSA fullthickness scalding on murine splenic T lymphocyte phosphoinositide-specific PLC signal pathway and its function

目的 :探索 18%Ⅲ度烫伤对小鼠脾脏T淋巴细胞肌醇脂质信号系统活性的影响及其与T细胞功能受抑 ,IL 2、IL 10分泌的关系 ,即烧伤后T淋巴细胞功能受抑的信号转导分子机制。方法 :以 18%Ⅲ度烫伤小鼠为模型 ,检测烫伤后不同时相参与跨膜信号转导的G蛋白 (G protein)、蛋白酪氨酸激酶 (PTK)、蛋白激酶C(PKC)及胞浆PTK、PKC、PI PLC活性与Ca+ + 浓度的改变 ,观察不同时相细胞功能及IL 2、IL 10分泌 ,分析各信号转导分子活性改变与T细胞功能受抑 ,IL 2、IL 10分泌的关系。结果 :烧伤后膜G protein、浆PI PLC酶活性受到抑制 (G protein活性明显降低出现于伤后 2h ,P <0 0 5 ,显著降低持续到伤后96h ,P <0 0 1;浆PI PLC变化趋势与G protein相同 ,但出现活性受抑的时间较G protein拖后一个时相 )。胞浆游离Ca+ + 浓度明显降低 ,明显降低的时相亦始于伤后 12h。PTK和PKC由于存在膜浆两相 ,其变化规律较复杂 ,转膜PKC活性呈现先降低(伤后 2～ 2 4h)后升高 (伤后 96h及以后 )的双相改变 ,浆PKC活性变化与之相反 ;膜PTK活性于伤后早期降低 ,16 8h后升高 ,浆PTK活性于伤后各时相均升高。T淋巴细胞增殖能力和IL 2分泌于伤后各时相均降低 ,其变化趋势与胞膜G protein和胞浆游离Ca+ + 浓度呈显著正性直线相关。IL 10分?

Objective:To investigate the changes of postburn activity on murine splenic T lymphocyte phosphoinositide-specific PLC signal pathway, and look for the relationship between the postburn and T cell function suppression, IL-2 and IL-10 secretion.Methods:The experimental model was 18% TSBA (total body surface area) fullthickness scalded mice by vapor. The activities of G-protein, PTK (membrane, cytoplasmic) PKC (membrane, plasmic),PI-PLC and cytoplasmic free calcium concentration were detected at different postburn periods, moreover T lymphocyte proliferating function, IL-2 and IL-10 secretion were examined.Results:Compared with control group, membrane GTPase and plasmic PI-PLC enzyme were suppressed after scalded, calcium concentration lowered down significantly, the activities of PTK and PKC were complex, membrane PKC activity elevated after decreasing, those of plasmic PKC were just on the contrary, and the total activity of membrane and plasmic PKC was not stable; Membrane PTK activity decreased in the postburn early stage, then increasing.T cells proliferating function and IL-2 production marginally reduced, and the depressed levels of IL-2 production and T cells proliferating activity were positive parallel with the activities of G-protein and Ca ++. Cytoplasmic PKC activity lowered down after elevating, which was just negative linearly correlated with IL-10 secretion.Conclusion:Inhibition of G-protein ?PTK and Ca ++ activities in phosphoinositide-specific PLC signal pathway was the main reason which resulted in the decrease of IL-2 secretion, suppressed T cell proliferation and the dual-directional changes in IL-10 secretion.