基于肠-肾轴角度论免疫球蛋白A肾病中西医发病机制及治疗进展

A review on the pathogenesis and the treatment of IgA nephropathy in TCM and Western medicine from the perspective of gut-kidney axis

免疫球蛋白A(Immunoglobulin A,IgA)肾病是目前我国发病率最高的原发性肾小球疾病之一,为自身免疫性疾病,以循环中半乳糖缺乏的IgA1(Galactose-Deficient IgA1,Gd-IgA1)水平升高和系膜区免疫复合物沉积为主要特征。Gd-IgA1主要来源于肠道相关淋巴组织(Gut Associated Lymphoid Tissue,GALT)并引发肠道黏膜过度免疫反应,肠道功能失调与肾脏疾病相互影响,由此形成“肠-肾轴”理论。一方面,肠道生态环境失调破坏肠道屏障,导致肠内毒素增加,进而引发全身性炎症反应,加重肾脏损伤;另一方面,肾脏功能失调导致肠循环中尿毒症毒素沉积,打破肠道微生物环境平衡。两者互为因果,相互影响,抑制GALT中过度的黏膜免疫反应有助于重建肠道微环境,维持肠道黏膜正常免疫,进而减轻肾脏损伤。近年来,基于肠-肾轴理论衍生了新兴治疗方法,例如肠道靶向免疫调节剂、益生菌等药物,可有效维持肠道微环境平衡。同时,中医药在稳定肠道免疫功能、重建肠道屏障、纠正肠道菌群等方面具有显著疗效,临床多根据患者病情采用通腑祛浊、扶正祛邪等阶段化特异性治疗,以有效延缓IgA肾病的进展,稳定患者病情。研究基于肠-肾轴角度,结合肠道黏膜免疫、肠道菌群,对IgA肾病中西医发病机制及新兴治疗成果进行综述,揭示肠-肾轴在IgA肾病的发生发展过程中的重要地位,为中西医结合治疗IgA肾病提供新策略。

Immunoglobulin A nephropathy is one of the primary glomerular diseases with the highest incidence in China.IgA nephropathy,as an autoimmune disease,is characterized by elevated circulating levels of galactose-deficient IgA1(Gd-IgA1)and immune complex deposition in the mesenteric region.Gd-IgA1 mainly originates from the gut-associated lymphoid tissue(GALT)and triggers an excessive immune response in the intestinal mucosa.Gd-IgA1 is mainly derived from GALT and triggers an excessive immune response in the intestinal mucosa.Intestinal dysfunction interacts with renal disease,resulting in the formation of the theory of gut-kidney axis.On the one hand,the dysregulation of intestinal ecological environment destroys the intestinal barrier,leading to the increase of intestinal endotoxins,which in turn triggers a systemic inflammatory response and aggravates renal injury.On the other hand,renal dysfunction leads to the deposition of uremic toxins in the intestinal circulation,which destroys the positive balance of the intestinal microbial environment.These two factors are mutually causal and influence.Inhibiting the excessive mucosal immune response in GALT is conducive to the reconstruction of intestinal microenvironment,and can maintain normal intestinal mucosal immunity,thereby reducing kidney injury.In recent years,based on the theory of gut-kidney axis,new therapeutic methods have been derived,such as intestinaltargeted immunomodulators,probiotics and other drugs,which can effectively maintain the balance of the intestinal microenvironment.Meanwhile,traditional Chinese medicine(TCM)shows significant therapeutic effects in stabilizing intestinal immune function,rebuilding the intestinal barrier,correcting the intestinal bacterial flora,etc.In clinical practice,according to disease condition,the method of clearing Fu(腑)organs and removing turbidity is mainly used to strengthen the body resistance and eliminate pathogenic factors,which effectively delays the progression of IgA nephropathy and stabilizes the disease condition.In this paper,combined with intestinal mucosal immunity and intestinal flora,the pathogenesis of IgA nephropathy in TCM and Western medicine and the emerging therapeutic achievements are reviewed from the perspective of gut-kidney axis,which reveals the importance of gut-kidney axis in the process of IgA nephropathy,and provides a new strategy for the treatment of IgA nephropathy in TCM and Western medicine.