A20蛋白水平影响狼疮模型小鼠TLR2、4-p38MAPK/NF-kB信号通路的初步研究

Effect of A20 protein level on TLR2,4-p38MAPK/NF-kB signaling pathway in lupus model mice

目的探讨PBMC中高水平的A20(TNFAIP3)蛋白能否抑制TLR2、4-p38MAPK/NF-κB信号通路并缓解SLE小鼠的炎症反应。方法观察MRL/lpr小鼠瑞香素(Daphnetin)处理组一般情况和生存期,检测其尿蛋白含量;检测血清中BUN、antidsDNA IgG、IL-6和TNF-α水平;检测PBMC裂解液中A20、TLR2、TLR4、pNFκB-p65及pp38MAPK水平。以上所有指标均与MRL/lpr小鼠未处理组、阴性对照组BALB/c雌性小鼠进行比较。结果随着Daphnetin处理组小鼠PBMC裂解液中A20蛋白水平显著升高(P<0.01),小鼠尿蛋白及血清BUN减少(P<0.001,P<0.001),其生存期(存活率)虽低于阴性对照健康鼠,但明显优于未处理组狼疮鼠(66.7%<88.9%<100%);血清中anti-dsDNA IgG、IL-6和TNF-α水平明显下降(P<0.01,P<0.01,P<0.001);PBMC裂解液中TLR2、TLR4、pNFκB-p65、pp38MAPK水平均有明显下降(P均<0.05)。结论PBMC中A20水平升高可抑制TLR2、4-p38MAPK/NF-κB信号通路,从而明显改善对MRL/lpr狼疮模型小鼠的炎症反应。

Objective To investigate whether the high level of A20(TNFAIP3)protein in PBMC can inhibit the TLR2,4-p38MAPK/NF-κB signaling pathway and alleviate the inflammatory response in SLE mice.Methods Observe the general condition and survival time of MRL/lpr mice in Daphnetin treatment group,and measure their urine protein content;detect the levels of BUN,anti-dsDNA IgG,IL-6 and TNF-αin serum;detect A20,TLR2,TLR4,pNFκB-p65 and pp38MAPK levels in PBMC lysate.Meanwhile,all the above indexes were compared with MRL/lpr mice in the untreated group and BALB/c female mice in the negative control group.Results With the increase of A20 protein level in PBMC lysate of mice in Daphnetin treatment group(P<0.01),the urine protein and serum BUN of mice decreased(P<0.001,P<0.001),and the hair,body weight and survival rate were significantly better than those in untreated group(66.7%<88.9%<100%).Serum levels of anti-dsDNA IgG,IL-6 and TNF-αdecreased significantly(P<0.01,P<0.01,P<0.001);the levels of TLR2,TLR4,pNFκB-p65、pp38MAPK in the PBMC lysate significantly decreased(all P<0.05).Conclusion A20 levels can inhibit the TLR2,4-p38MAPK/NF-κB signaling pathway and thus significantly relieve the inflammatory response to MRL/lpr lupus model mice.