邓璇, 王瑜. Toll样受体4与Nod样受体蛋白3炎性小体在糖尿病肾脏疾病中的研究进展[J]. 临床肾脏病杂志, 2022, 22(7): 595-601. DOI: 10.3969/j.issn.1671-2390.2022.07.011
    引用本文: 邓璇, 王瑜. Toll样受体4与Nod样受体蛋白3炎性小体在糖尿病肾脏疾病中的研究进展[J]. 临床肾脏病杂志, 2022, 22(7): 595-601. DOI: 10.3969/j.issn.1671-2390.2022.07.011
    Deng Xuan, Wang Yu. Research advances of role of TLR4/NLRP3 inflammasome in diabetic nephropathy[J]. Journal of Clinical Nephrology, 2022, 22(7): 595-601. DOI: 10.3969/j.issn.1671-2390.2022.07.011
    Citation: Deng Xuan, Wang Yu. Research advances of role of TLR4/NLRP3 inflammasome in diabetic nephropathy[J]. Journal of Clinical Nephrology, 2022, 22(7): 595-601. DOI: 10.3969/j.issn.1671-2390.2022.07.011

    Toll样受体4与Nod样受体蛋白3炎性小体在糖尿病肾脏疾病中的研究进展

    Research advances of role of TLR4/NLRP3 inflammasome in diabetic nephropathy

    • 摘要: 慢性肾脏病发病率逐年上升,现已成为威胁全世界公共健康的主要疾病之一。导致慢性肾脏病的基本病因众多,主要包括原发性与继发性肾小球肾炎、糖尿病肾脏疾病、高血压肾损害、肾小管间质病变、遗传性疾病等。而糖尿病肾脏疾病作为慢性肾脏病的病因之一,是糖尿病引起的肾脏微血管病变的并发症,不加以控制可进展为终末期肾病。糖尿病肾脏疾病的具体发病机制尚不完全清晰,主要以高糖等代谢因素导致的免疫介导性炎症对肾脏破坏为主,而近年来发现免疫介导性炎症因素是糖尿病肾脏疾病发生的重要原因之一。在糖尿病肾脏疾病中,机体处在高糖状态下募集如白介素、肿瘤坏死因子等炎症反应细胞在肾脏浸润,从而刺激肾脏微血管病变的发生,这一过程涉及多种信号通路的发生。在天然免疫应答系统中,Toll样受体4(toll like receptor 4,TLR4)以及Nod样受体蛋白3(nod-like receptor family pyrin domain-containing protein 3,NLRP3)炎性小体在肾脏相关免疫炎症疾病中扮演着重要角色。近来研究发现,TLR4以及NLRP3炎性小体与糖尿病肾脏疾病的发病机制密切相关。在高糖条件下可检测到TLR4水平的增高,而TLR4通过识别特异性配体激活核因子κB(nuclear factor-κB,NF-κB)从而激活下游炎症因子的成熟与释放,进一步促进肾脏病变。NLRP3炎性小体在糖尿病患者肾脏的足细胞、系膜细胞等少量存在,NF-κB的活化激活炎性小体的组装与成熟,从而促进炎症因子的释放。因此,TLR4、NLRP3在糖尿病肾脏疾病的发生、发展中发挥着重要作用,本文就这一研究展开相关的阐述。

       

      Abstract: The incidence of chronic kidney disease(CKD)has been rising yearly. And it has become one of the major hazards to public health in the world. The underlying causes of CKD include primary/secondary glomerulonephritis,diabetic nephropathy,hypertensive renal damage,renal tubulointerstitial lesions and genetic disorder,etc. Diabetic kidney disease(DKD),one of the causes of CKD,is a complication of diabetic renal microangiopathy and end-stage renal disease ensues if left unchecked. The specific pathogenesis of DKD has remained elusive. Hyperglycemia causes immune-mediated inflammation and renal injuries. However,immune-mediated inflammatory factors are one of the important causes of DKD. During hyperglycemia,such inflammatory response cells as interleukin and tumor necrosis factors are mobilized to infiltrate kidney and stimulate the development of renal microangiopathy through a large variety of signaling pathways. In recent years,Toll-like receptor 4(TLR4)and NoD-like receptor family pyrin domain-containing protein 3(NLRP3)play an important role in renal-related immune inflammatory diseases. And TLR4/NLRP3 inflammatory bodies are closely correlated with the pathogenesis of DKD. Elevated TLR4 level has been detected under hyperglycemia. However,TLR4 stimulates the maturation and release of downstream inflammatory factors by activating NF-κB through recognizing specific ligands and NLRP3 inflammatory bodies exist sparsely in mesangial cells of DKD. The activation of NF-κB activates the assembly and maturation of inflammatory bodies,thus promoting the release of inflammatory cytokines. Thus TLR4 and NLRP3 play some important roles in the development of diabetic nephropathy.

       

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