[Therapeutic effect and mechanism of Qingxin Lianzi Decoction in ameliorating diabetic kidney disease based on renal metabolomics].

Renal metabolomics and molecular biology techniques were employed to investigate the interventional effect and underlying mechanism of Qingxin Lianzi Decoction(QXLZ) in rats with diabetic kidney disease(DKD). Sprague-Dawley rats were randomly assigned to the following groups: a blank group, a model group, a metformin(0.2 g·kg~(-1)) group, and QXLZ low-, medium-, and high-dose groups(10, 20, and 40 g·kg~(-1), respectively). The DKD model was established in all groups except the blank group by feeding with a high-fat diet combined with intraperitoneal injection of streptozotocin(STZ, 30 mg·kg~(-1)). After successful modeling, the rats received the corresponding treatments by oral gavage for six consecutive weeks. Upon completion of the intervention, random blood glucose levels were measured to assess the glucose-regulating capacity of QXLZ in DKD rats. Renal histopathological changes and fibrosis degree were evaluated by hematoxylin-eosin, Masson's trichrome, and periodic acid-Schiff staining. Renal function indicators(24-hour urinary total protein [24h-UTP], blood urea nitrogen [BUN], creatinine [Cr]) were measured by biochemical assays. The levels of blood glucose(glycated hemoglobin [GHb]), inflammatory markers(tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β]), and fibrosis markers(collagen type Ⅳ [Col Ⅳ], α-smooth muscle actin [α-SMA]) were detected by enzyme-linked immunosorbent assay. Immunofluorescence was used to determine the expression of TNF-α, IL-1β, α-SMA, and Col Ⅳ in renal tissues. Metabolomics was applied to identify differentially expressed metabolites in renal tissues. The results showed that compared with the blank group, the model group showed significant increases in several key indicators, including random blood glucose and GHb reflecting glucose metabolism, 24h-UTP, BUN, and Cr assessing renal function, as well as the inflammatory cytokines TNF-α and IL-1β and the fibrosis markers Col Ⅳ and α-SMA(P<0.05). The renal histology also exhibited typical features of DKD. Compared with the model group, all intervention groups showed significant reductions in these indicators, along with decreased collagen deposition and inflammatory resolution. Metabolomic analysis revealed that the intervention of QXLZ in DKD was closely associated with the arachidonic acid metabolism pathway. In conclusion, QXLZ effectively regulates blood glucose, improves renal function, and ameliorates renal inflammation and fibrotic injury in DKD rats, and its mechanism may be related to the arachidonic acid metabolic pathway.