端粒保护蛋白复合体在原发性痛风性关节炎患者转录水平的变化及其意义

目的探讨端粒保护蛋白在痛风性关节炎（GA）炎症及免疫中可能的作用。方法应用实时荧光定量聚合酶链反应检测42例GA患者（GA组）及38名健康体检者（NC组）外周血单个核细胞端粒保护蛋白复合体（TRF1、TRF2、TPP1、POT1、TIN2和hRAP1）、NLRP3炎性体（NLRP3、ASC和Caspasel）及凋亡相关蛋白（BCL2和BAX）mRNA水平，并且与GA患者临床指标进行相关性分析。结果TPP1、POT1及TIN2mRNA在GA组的表达显著低于NC组（P均〈0．05），TRF1、TRF2显著高于NC组（P均〈0．05）；炎性体成分ASCmRNA在GA组显著高于NC组（P〈0．01），NLRP3、CaspaselmRNA则低于NC组（P均〈0．05）；hRAP1、BCL2及BAXmRNA在两组表达的差异均无统计学意义（P均〉0．05）。GA患者TRF1mRNA与ASC，TPP1mRNA与ASC，TIN2mRNA与中性粒细胞计数，TRF2mRNA与GLOB，NLRP3mRNA与BCL2、BAXmRNA均呈正相关（P均〈0．05）；而TPP1mRNA与NLRP3、BCL2、BAXmRNA，TRF2mRNA与NLRP3mR-NA，POT1mRNA与uA、apoA1，TIN2 mRNA与apoA1，TRF2mRNA与apoA1均呈负相关（P均〈0．05）；其余临床及实验室指标间均无相关性（P均〉0．05）。结论端粒保护蛋白相关成分的异常表达可能参与了痛风免疫、炎症及代谢过程。TPP1、TIN2、TRF1和TRF2同时参与了痛风炎症与免疫调节，且相互影响、相互制约；TPP1与NLRR3可能同时参与了痛风促凋亡与抗凋亡平衡的调节；POT1、TIN2和TRF2则可能在痛风患者的尿酸及脂代谢中发挥作用。

Altered expression of telomere shelterin complex might play a role in the pathogenesis of primary gouty inflammation

Objective To explore the telomere shelterin complex and NLRP3 inflammasome changes, and evaluate the clinical significance of the changes in patients with gouty arthritis （GA）. Methods Telomere shelterin complex（ including TRF1, TRF2, TPP1, POT1, TIN2 and hRAPI ）, NLRP3 inflammasome （ including NLRP3, ASC and Caspasel ） and apoptosis-associated protein （ including BCL2 and BAX） mRNA was measured using real-time polymerase chain reaction（RT-PCR） in the peripheral blood mononuclear cells （PBMC）from 42 patients with GA and 38 healthy individuals （ as normal control, NC ） ; correlations between the mRNA expression levels and clinical, laboratory data were analyzed. Results The expression of TPP1, POT1, TIN2, NLRP3 and Caspasel mRNA was significantly reduced in GA patients compared with the NC subjects （ P 〈 0. 05, respectively）, contrasting with the higher expression of TRF1 ,TRF2 and ASC mRNA（P 〈 0. 05 ,respectively）;no significant difference was found in hRAPI, BCL2 and BAX mRNA（P 〉 0.05, respectively）. Significant positive correlations were found between levels of TPP1 mRNA and ASC, TRF1 mRNA and ASC, TIN2 mRNA and neutrophil counts, TRF2 mRNA and globulin, NLRI~ mRNA and BCL2, BAX mRNA（P 〈 0. 05, respectively）, but negative correlations between levels of TPP1 mRNA and NLRP3, BCL2, BAX, POT1 mRNA and uric acid, apoA1, TIN2 mRNA and apoA1, TRF2 mRNA and apoA1 （P 〈 0.05, respectively） were observed in GA patients. Conclusion Altered expression of telomere shelterin complex and NLRP3 inflammasome mRNA might be involved in the pathogenesis of gouty inflammation.