基于肠源性微炎症探讨糖尿病肾脏病“内热致癥”病机的科学内涵

The Pathogenesis of Collateral Conglomeration induced by Endogenous Heat is the core mechanism of Diabetic Kidney Disease.Enterogenous microinflammation is the main source of Endogenous Heat. Previously it was proved that Shen-Yan-Fang-Shuai Formula (SYFSF) functioned as anti-inflammation and anti-fibrosis,Meanwhile, it regulated the structure of the Gut Microbiota and decreased the concentration of serum LPS of DKD rats. Thus we propose the hypothesis that SYFSF may play a role in anti-inflammation through regulating the Enterogenous Microinflammation and inhibiting the TLRs/NF-κB pathway of renal intrinsic cells. Our research plans to explore the balancing effect of SYFSF on gut microbiota by DKD rats and further proved in DKD patients,then explore the mechanism by feces transplantation from the gut microbiota composition, permeability of intestinal mucosa, and the expression of TLRs/NF-κB pathway in renal intrinsic cells, as well as the related gut bacteria,so as to further define the functional mechanism of SYFSF in microbial level and enrich the scientific connotation of the pathogenesis about collateral conglomeration induced by endogenous heat in Diabetic Kidney Disease.

“内热致癥”是糖尿病肾脏病（DKD）的核心病机，肠源性微炎症是DKD“内热”的重要来源。前期研究证实基于该病机的肾炎防衰液对DKD模型大鼠具有抗炎抗纤维化作用，并初步发现可以改善该模型大鼠肠道菌群结构，降低血清LPS水平。据此，本研究提出“肾炎防衰液可能通过改善肠源性微炎症进而抑制肾脏固有细胞TLRs/NF-κB通路活化从而延缓DKD进展”的假说。在前期小样本研究基础上，本研究拟扩大动物样本阐明肾炎防衰液能否改善DKD模型大鼠肠道菌群丰度、降低变形菌等致炎菌比例，富集乳酸菌等有益菌，并在DKD患者中加以验证；然后以粪便移植方法反证肾炎防衰液的抗炎作用是否与调节菌群、降低肠黏膜通透性相关，并筛查相关菌种；最后探讨肾炎防衰液的肾保护作用是否与抑制肾脏固有细胞TLRs/NF-κB通路有关，进而从肠道微生态平衡角度阐明肾炎防衰液抗炎及肾保护作用的内在机制，揭示DKD“内热致癥”病机的科学内涵。

“内热致癥”是糖尿病肾脏病（DKD）的核心病机，肠源性微炎症是DKD“内热”的重要来源。团队基于前期研究提出了“基于内热致癥病机的QRXZF可能通过改善肠源性微炎症进而抑制肾脏固有细胞TLRs/NF-κB通路活化从而延缓DKD进展”的假说。本研究临床部分证实了LPS可能为DKD“内热”的物质基础，并作为重要的炎症物质，在DKD早期患者尿蛋白进展中起到重要作用；动物实验进一步证实了QRXZF通过调节肠道菌群紊乱、改善肠道粘膜通透性及抑制菌群紊乱介导的LPS/TLR4/NF-κB炎症通路，进而减轻DKD肾损伤。从肠道微生态平衡角度阐明了基于内热致癥病机的中药复方抗炎及肾保护作用的内在机制，揭示了DKD“内热致癥”病机的科学内涵。