Transcriptomics and Proteomics Reveal That TLPW Acupuncture Ameliorates Proteinuria in Diabetic Kidney Disease Model Rats by Suppressing Epithelial‐to‐Mesenchymal Transition via the DPP4/SDF‐1α/TGF‐β/Smad Signalling Axis

Ten male Sprague–Dawley rats were randomly assigned to serve as the negative control (NC) group, and 50 others were maintained on a high‐fat diet (HFD). After 18 weeks of feeding, the HFD group received streptozotocin (STZ) intraperitoneally to establish a DKD model. HFD group rats (24‐h urinary protein excretion rate ≥ 30 mg) were randomly divided into model (DKD), tiaolipiwei acupuncture (DKD + Acu, acupuncture for 30 min), AMD3100 (DKD + AMD3100, AMD3100 intraperitoneal injection) and tiaolipiwei acupuncture + AMD3100 group (DKD + Acu + AMD3100, AMD3100 intraperitoneal injection combined with tiaolipiwei acupuncture for 30 min) groups. The intervention lasted 4 weeks, and body weight and random blood glucose levels were recorded for each group before treatment each week. Postintervention (at 4 weeks), urine was collected to assess urinary protein–creatinine ratios, 24‐h urinary protein contents and urinary podocyte injury–related enzyme levels. Renal cortex tissues from three to five rats in the control, DKD and DKD + Acu groups were sent for transcriptomic and proteomic analyses, and renal tissues were collected for analyses of pathological indicators and mechanisms. Twenty‐four‐hour Upro, 24‐h urinary Spondin 2 (SPON2) levels, UACRs and random serum creatinine, urea nitrogen and blood glucose levels in the DKD + Acu group exhibited significantly reduced levels compared to the DKD group (# p < 0.05). According to the transcriptomic 2.2.2s and proteomic results, immunofluorescence or western blotting was used to assess podocyte‐specific marker expression levels (nephrin, podocin and CD2AP), epithelial–mesenchymal transition (EMT) markers (desmin, Fsp1 and α ‐SMA) and DPP‐4/SDF‐1 α /TGF‐ β /Smad signalling axis components; nephrin, podocin and CD2AP expression significantly elevated (# p < 0.05 or ## p < 0.01) and desmin, Fsp1 and α ‐SMA expression greatly decreased (# p < 0.05 or ## p < 0.01) in the DKD + Acu group. Tiaolipiwei acupuncture regulated the Dpp‐4/SDF‐1 α /TGF‐ β /Smad signalling axis (# p < 0.05 or ## p < 0.01), but this effect was reduced by AMD3100 (@ p < 0.05 or @@ p < 0.01). Tiaolipiwei acupuncture modulates the DPP‐4/SDF‐1 α /TGF‐ β /Smad signalling axis to inhibit podocyte EMT and alleviate podocyte and renal injury, ultimately ameliorating proteinuria in DKD model rats.