Herbal-Cake-Separated Moxibustion Ameliorates Renal Fibrosis and Associated Bone Injury in Rats via the TGF-β1/Smad Signaling Pathway.

Renal fibrosis is the main pathological basis for chronic kidney disease (CKD) progression and is often accompanied by decreased bone density and impaired bone microstructure. The TGF-β1/Smad signaling pathway may be a common intervention target for kidney and bone injury. This study evaluated the effects of herbal-cake-separated moxibustion (HCSM) on renal fibrosis and bone damage in CKD rats and explored its potential mechanism. CKD was induced by adenine gavage combined with a high-protein diet. Successfully modeled rats were randomly assigned to model, HCSM, and SIS3 groups (n = 6 each), with an additional control group (n = 6). The control and model groups received no intervention. The HCSM group received treatment at Pishu (BL20) and Shenshu (BL23), whereas the SIS3 group received intraperitoneal SIS3 (2.5 mg/kg every 2 days). Treatment comprised three 12-day courses separated by 2-day intervals. Renal injury was assessed by kidney function, kidney index, and histopathology. Western blotting measured TGF-β1, Smad2/3, p-Smad2/3, and BMP-7 expression, and micro-computed tomography assessed femoral bone density and microstructure. Compared with controls, model rats showed significantly increased blood urea nitrogen (BUN), serum creatinine (Scr), and kidney index (p < 0.0001); marked renal fibrosis; increased TGF-β1, p-Smad2/3, and Smad2/3; decreased BMP-7; reduced bone mineral density (BMD) and trabecular number; and increased trabecular separation. Compared with the model group, HCSM and SIS3 improved renal function and histopathology, increased BMD and trabecular number, reduced trabecular separation, suppressed TGF-β1/Smad signaling, and increased BMP-7 expression. These findings indicate that HCSM may improve renal fibrosis and associated bone damage by enhancing BMP-7 expression and inhibiting TGF-β1/Smad signaling.