高甘油三酯血症对血小板CD40L表达的影响及非诺贝特的作用

Effects of hypertriglyceridemia and fenofibrate on CD40L expression in platelets

目的:观察高甘油三酯(triglyce ride,TG)血对体内及体外血小板CD40L表达的影响及非诺贝特的作用。方法:以TG正常的健康对象为对照,通过流式细胞仪及ELISA法检测高TG患者服用非诺贝特前后血小板膜CD40L表达阳性率及血浆sCD40L表达;然后通过高TG血浆体外孵育健康血小板并用过氧化物酶体增殖活化受体α(PPARα)激动剂WY14643干预,流式细胞仪及Westen blotting法检测血小板膜CD40L表达阳性率及血小板总CD40L蛋白含量。结果:高TG患者CD40L及sCD40L表达显著升高(2.65±0.75vs1.53±0.66,3.72±0.94vs2.27±0.72),服用非诺贝特1个月后随TG浓度降低,血小板膜CD40L表达阳性率及血浆sCD40L浓度均有不同程度降低(1.89±0.56vs2.65±0.75,2.85±0.74vs3.72±0.94);体外高TG血浆较TG正常血浆更能促进血小板膜CD40L的表达(2.81±0.48vs1.89±0.41),且血小板总CD40L蛋白含量也一定程度升高(1.79±0.13vs1.51±0.15,P<0.05);但WY14643对体外血小板膜CD40L表达阳性率及CD40L含量均无显著影响。结论:高浓度的TG血浆体内体外均能够促进血小板CD40L的表达;PPARα激动剂非诺贝特在降低体内TG浓度的同时,也抑制了血小板CD40L的表达;但PPARα激动剂Wy14643体外无直接改变血小板CD40L表达的作用。

AIM： To observe the effects of hypertriglyceridemia and fenofibrate on CD40L expression in platelets in vitro and in vivo. METHODS： In vivo experiments, according to its own strict standards, 20 patients were respectively selected for hypertriglyceridemia group and control group, before and after treatment of fenofibrate for hypertriglyceridemia patients. The CD40 ligand positive rates of platelets by flow cytometry and plasma soluble CD40 ligand by ELISA were examined under the same conditions as control group. The CD40L and sCD40L in each group were compared. In in vitro experiments, all 6 objects plasma was chosen in the same condition except for triglyceridemia, after the co-incubation of these plasma with the same healthy platelets was performed and the interference with wy14643, the CD40 ligand positive rate of platelets by flow cytometry and total platelets CD40 ligand protein content by Western blotting were examined under the same conditions in all objects. The CD40L positive rate and total CD40L content in each group were compared, respectively. RESULTS： The platelet CD40L positive rate and plasma sCD40L concentration in hypertriglyceridemia group were significant higher than those in control group （P〈0.01）. Followed the TG concentration decreased, the platelet CD40L positive rate and plasma sCD40L concentration decreased after the treatment of fenofibrate, the same as the total platelets CD40L content which was significant higher in hypertriglyceridemia group than that in control group in vitro （P〈0.05）. No effect of wy14643 on the total CD40L content expression was observed in vitro. CONCLUSION： Hypertriglyceridemia plasma stimulates immune-activation of platelets both in vitro and in vivo. sCD40L may mainly come from CD40L on platelet membrane. PPARα activator of fenofibrate may inhibit the immune-activation of platelets by reducing the concentration of plasma TG, but PPARα activator WY14643 cant inhibit the expression of CD40L and CD40L in vitro.