紫癜性肾炎患者外周血单个核细胞Toll样受体3和4的信号转导途径

背景：目前关于Toll样受体3和Toll样受体4介导的信号转导通路在紫癜性肾炎的发病机制中的作用尚不清楚。目的：分析Toll样受体3和Toll样受体4在过敏性紫癜和紫癜性肾炎发病机制中的作用。方法：选取过敏性紫癜患儿64例，分为过敏性紫癜无肾损害组36例及过敏性紫癜性肾炎组28例，另选健康儿童30例作为正常对照组。实时荧光定量PCR检测外周血单核细胞Toll样受体3、Toll样受体4、髓样分化蛋白2、髓样细胞分化因子88、白细胞介素1β、白细胞介素6、白细胞介素12 mRNA的基因相对表达量；应用流式细胞术检测外周血单核细胞Toll样受体3、Toll样受体4蛋白表达率。结果与结论：①过敏性紫癜患儿Toll样受体4 mRNA及蛋白表达显著高于正常对照组（P 〈 0.05）。紫癜性肾炎组Toll样受体4 mRNA及蛋白表达均显著高于紫癜无肾损害组（P 〈 0.05）。②过敏性紫癜组髓样分化蛋白2、髓样细胞分化因子88、白细胞介素1β、白细胞介素6 mRNA的表达均显著高于正常对照组（P 〈 0.05），白细胞介素12 mRNA的表达显著低于正常对照组（P 〈 0.05）；紫癜性肾炎组髓样分化蛋白2、髓样细胞分化因子88、白细胞介素1β、白细胞介素6 mRNA的表达显著高于紫癜无肾损害组（P 〈 0.05），紫癜性肾炎组白细胞介素12 mRNA的表达显著低于紫癜无肾损害组（P 〈 0.05）。③过敏性紫癜组患儿外周血单核细胞Toll样受体4 mRNA与蛋白表达呈正相关（r=0.60，P 〈 0.01）；过敏性紫癜患儿Toll样受体4 mRNA与髓样分化蛋白2、髓样细胞分化因子88、白细胞介素1β、白细胞介素6表达均呈正相关（P 〈 0.01），与白细胞介素12 mRNA表达呈负相关（r=-0.66，P 〈 0.01）。提示Toll样受体4可能通过髓样细胞分化因子88依赖信号转导途径介导过敏性紫癜的免疫发病机制，Toll样受体4的过度活化可能与过敏性紫癜的肾损伤有关。

Toll-like receptor 3 and Toll-like receptor 4 signal transduction pathways in the peripheral blood mononuclear cells of purpura nephritis patients

BACKGROUND： Toll-like receptor 3 and Toll-like receptor 4 may be play a significant role in the pathogenesy of many diseases about the renal, but, at present, the influence of Toll-like receptor 3 and Toll-like receptor 4 signal transduction pathway in children with Henoch-Sch0nlein purpura nephritis has been unknown. OBJECTIVE： To investigate the mechanism of Toll-like receptor 3 and Toll-like receptor 4 in Henoch-SchOnlein purpura and Henoch-Sch~nlein purpura nephritis. METHODS： Totally 64 children with a clinical diagnosis of Henoch-Sch6nlein purpura were enrolled in the study and divided into two groups, 36 children with non-Henoch-SchOnlein purpura nephritis and 28 children with Henoch-SchOnlein purpura nephritis. Another 30 healthy age-matched children served as controls. The relative expression levels of Toll-like receptor 3, Toll-like receptor 4, myeloid differentiation protein 2, myeloid differentiation factor 88, interleukin-ll3, interleukin-6, interleukin-12 mRNA in peripheral blood mononuclear cells were detected by real-time fluorescent PCR. Protein levels of Toll-like receptor 3 and Toll-like receptor 4 were detected by flow cytometric analysis. RESULTS AND CONCLUSION： （1） Compared with the control group, the relative expression levels of Toll-like receptor 4 mRNA and protein were remarkably increased in children with Henoch-SchOnlein purpura （P 〈 0.05）; compared with the children with non-Henoch-Sch5nlein purpura nephritis, the relative expression levels of Toll-like receptor 4 mRNA and protein were remarkably increased in children with Henoch-Sch6nlein purpura nephritis （P 〈 0.05）. （2） Compared with the control group, mRNA expression levels of myeloid differentiation protein 2, rnyeloid differentiation factor 88, interleukin-113, and interleukin-6 were remarkably increased in children with Henoch-Sch6nlein purpure （P 〈 0.05）, while interleukin 12 mRNA expression level was remarkably decreased （P 〈 0.05）. Compared with the children with non-Henoch-SchOnlein purpura nephritis, the mRNA expression levels of myeloid differentiation protein 2, myeloid differentiation factor 88, interleukin-1β, and interleukin-6 were remarkably increased in children with Henoch-Schonlein purpura nephritis （P 〈 0.05）, while the mRNA expression of interleukin 12 was remarkably decreased （P 〈 0.05）. （3） The mRNA expression of Toll-like receptor 4 showed a positive correlation with expressions of Toll-like receptor 4 protein （r=0.60, P 〈 0.01）, myeloid differentiation protein 2, myeloid differentiation factor 88, interleukin-113, and interleukin-6 mRNA （P 〈 0.01 ）, but negative with interleukin-12 mRNA （r=-0.66, P 〈 0.01）. These findings indicate that Toll-like receptor 4 activation may be involved in the pathogenesis of Henoch-Sch0nlein purpura and the excessive activation of Toll-like receptor 4 may be associated with the damage of kidney in the Henoch-SchOnlein purpura.