基于SCFAs/GPCRs/MCP-1通路研究健脾护肾汤对糖尿病肾病大鼠肾小管间质纤维化的影响

糖尿病肾病(DKD)是中国终末期肾病主要原因，明确DKD发病机制、寻找有效防治措施备受关注。健脾护肾汤广泛应用于DKD早中期治疗，疗效显著，但作用机制有待阐明。肠-肾轴理论认为肠道菌群失调加剧肠源性尿毒素合成，诱发全身微炎症，进一步损害肾功能，导致肠肾间恶性循环。可见，肠道微生态与肾脏病密切相关，但其与DKD联系仍不清楚。基于中医取类比象的象思维理论，肠道与肾小管结构、功能、病理相似，都是具有绒毛的中空管腔结构，传化物而不藏，泌别清浊。可能肠道与肾小管也有相同的信息交流，肠道产生的短链脂肪酸(SCFAs)经吸收进入循环系统，通过G蛋白偶联受体(GPCRs)参与肾脏免疫炎症反应，抑制单核细胞趋化因子(MCP-1)分泌，减轻肾小管间质纤维化，从而延缓DKD进展。本项目基于SCFAs/GPCRs/MCP-1通路，研究健脾护肾汤对DKD大鼠肾小管间质纤维化的影响，为中医药治疗DKD提供新的研究思路。

Diabetic kidney disease (DKD) is the main cause of End-stage Renal Disease in China.To clarify the pathogenesis of DKD and search for effective control measures has attracted much attention.Jianpi hushen decoction has been widely used in the early and middle treatment of DKD, with remarkable curative effect,but the mechanism of action remains to be clarified.The Gut-Kidney axis theory suggests that the imbalance of intestinal flora intensifies the synthesis of enterogenous urotoxin,induces systemic microinflammation,further damage renal function, and lead to a vicious cycle between the gut and kidney. It can be seen that intestinal microecology is closely related to renal disease, but the mechanism between intestinal microecology and DKD remains unclear. Based on the image thinking theory of analogy,intestinal and renal tubules are similar in structure,functional characteristics and pathological mechanism. Both of them are hollow lumen structures with villi,and they transferring things without hiding them, separating the clear from the turbid.Possible intestinal and renal tubular also have the same information exchange,short chain fatty acid(SCFAs) production in the gut by the absorption into the circulatory system, through the G protein coupled receptors (GPCRs) to participate in the kidney immune inflammation,inhibition monocyte chemoattractant protein-1(MCP-1) secretion,reduce renal tubular interstitial fibrosis,delay DKD progression. Based on the SCFAs/GPCRs/MCP-1 pathway, this project studied the effects of Jianpi hushen Decoction on renal tubulointerstitial fibrosis in DKD rats,and provided a new research idea for the treatment of DKD with traditional Chinese medicine.