肿瘤坏死因子超家族成员14调控炎症反应和脂质代谢的作用机制

Mechanism of Tumor Necrosis Factor Superfamily 14 on Inflammation and Lipid Metabolism

目的探讨肿瘤坏死因子超家族成员14(LIGHT)在脂质代谢中的作用,为高脂血症相关疾病的临床治疗提供参考。方法冠心病患者32例,其中不稳定型心绞痛组和稳定型心绞痛组各16例;健康人16例作为正常对照组。检测LIGHT在不同阶段冠心病患者中的表达变化,观察脂质代谢相关酶和炎症相关蛋白在氧化低密度脂蛋白(oxLDL)诱导单核巨噬细胞(THP-1)中的表达。结果LIGHT在冠心病患者中表达水平显著高于健康人;LIGHT增强清道夫受体(SR-A),乙酰辅酶A乙酰转移酶1(ACAT1),脂肪基因(SREBP-1c、ACS)和促炎细胞因子[白细胞介素(IL)-6、人单核细胞趋化蛋白-1(MCP-1)、一氧化氮合酶(iNOS)]的表达(P<0.05),该作用可被淋巴毒素β受体(LTβR-Ig)阻止;SN50显著抑制核转录因子(NF)-κB、p65、IL-6和脂肪基因的表达(P<0.05)。结论LIGHT通过激活NF-κB信号通路促进炎症反应和脂质累积,可为高脂血症相关疾病的治疗提供一个新的潜在靶点。

Objective To explore the role of tumor necrosis factor superfamily member 14(LIGHT)in lipid metabolism,and to provide references for clinical treatment of hyperlipidemia-related diseases.Methods A total of 32 patients with coronary heart disease took part in the trial,including 16 patients in the unstable angina group and 16 patients in the stable angina group.Sixteen healthy people served as the control group.The expression of LIGHT in patients with coronary heart disease at different stages was examined.The expression of lipid metabolism-related enzymes and inflammation-related proteins in oxidized low density lipoprotein(oxLDL)-induced mononuclear macrophages(THP-1)was observed.Results The expression level of LIGHT in patients with coronary heart disease was significantly higher than that in healthy people(P<0.05).LIGHT enhanced the expression of scavenger receptor(SR-A),acetyl-CoA acetyltransferase 1(ACAT1),adipose gene(SREBP-1c,ACS),interleukin-6(IL-6),human monocyte chemotaxis protein-1(MCP-1),and nitric oxide synthase(iNOS)(P<0.05).These effects could be blocked by the lymphotoxin beta receptor(LTβR-Ig).The NF-κB translocation inhibitor SN50 significantly inhibited the expression of nuclear transcription factors(NF)-κB,p65,IL-6 and adipose genes(P<0.05).Conclusion LIGHT promotes inflammatory response and lipid accumulation by activating NF-κB signaling pathway,which providing a new potential target for the treatment of hyperlipidemia-related diseases.