糖尿病肾病(diabetic nephropathy，DN)是糖尿病患者死亡的主要驱动因素，其患病率在全球范围内呈上升趋势。DN的发生发展与复杂的慢性低度炎症密切相关。在糖尿病患者中，高血糖和高血脂会导致损伤相关分子模式的释放，触发Janus激酶/信号转导与转录激活子3(Janus kinase/signal transducer and activator of transcription 3，JAK/STAT3)、核因子-κB(nuclear factor kappa-B，NF-κB)、磷脂酰肌醇 3 激酶(phosphatidylinositol-3-kinase，PI3K)-蛋白质激酶 B(protein kinase B，PKB或Akt)等促炎细胞信号通路的活化，以及白介素-1(interleukin-1，IL-1)、IL-6和肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)等促炎细胞因子的产生，这些促炎因子是导致肾损伤的关键致病介质，从糖尿病的初始阶段到晚期肾衰竭中均发挥着多重作用。迷走神经是自主神经系统的关键组成部分，其通过介导胆碱能抗炎通路(cholinergic anti-inflammatory pathway，CAP)发挥抗炎作用。在DN时，迷走神经活性下降，胆碱能抗炎系统受损，促炎与抗炎反应失调，肾的炎症和损伤加重。而利用神经免疫相互作用，通过迷走神经刺激术激活CAP，则可调控炎症信号通路及炎性细胞因子，改善DN的炎症和损伤状态。本文将对炎症细胞因子和炎症信号通路在DN发生发展中的作用，以及迷走神经活化的胆碱能抗炎通路对DN的改善作用进行综述，以期为DN等慢性炎症相关疾病的治疗策略研究及应用提供理论基础。
Role of the Vaginergic Activated Cholinergic Anti-inflammatory Pathway in Diabetic Nephropathy
Diabetic nephropathy(DN)is the main driver of deaths in diabetic patients,and its prevalence is increasing worldwide.The occurrence and development of DN is closely related to complex chronic low-grade inflammation.In diabetic patients,hyperglycemia and hyperlipidemia lead to the release of injury-related molecular patterns,triggering the activation of pro-inflammatory cell signaling pathways such as Janus kinase/signal transducer and activator of transcription 3(JAK/STAT3),nuclear factor kappa-B(NF-κB),and phosphatidylinositol-3-kinase(PI3K)-protein kinase B(PKB or Akt),and the production of pro-inflammatory cytokines such as interleukin-1(IL-1),IL-6 and tumor necrosis factor-α(TNF-α).The pro-inflammatory cytokines are key pathogenic agents leading to kidney injuries,which play multiple roles from the initial stage of diabetes to advanced renal failure.The vagus nerve is a key component of the autonomic nervous system and plays an anti-inflammatory role by mediating the cholinergic anti-inflammatory pathway(CAP).In DN,the activity of the vagus nerve is decreased,the cholinergic anti-inflammatory system is damaged,the pro-inflammatory and anti-inflammatory response is dysregulated,and the kidney inflammation and injury are aggravated.By activating CAP through stimulating the vagus nerve by neuroimmune interaction,inflammatory signaling pathways and inflammatory cytokines can be regulated,and inflammation and injury of DN can be improved.Here we review the role of inflammatory cytokines and inflammatory signaling pathways in the occurrence and development of DN and the improvement of DN by the cholinergic anti-inflammatory pathway activated by the vagus nerve,aiming to provide a theoretical basis for the research and application of treatment strategies for chronic inflammatory diseases such as DN.
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