Mitigation of renal microvascular injury in diabetic kidney disease model mice by electroacupuncture

Renal microvascular injury, as the result of diabetic toxicity, plays a vital role in the pathogenesis of diabetic kidney disease (DKD) during diabetes progression. Here, we investigated whether electroacupuncture (EA) could ameliorate renal microvascular impairment to prevent DKD and its underlying mechanism. The male db/db mice with Leprdb mutation were used as the model of type 2 diabetes mellitus-induced DKD and treated with EA at “Zusanli (ST36)” and “Weiwanxiashu (EX-B3)” acupoints for 4 weeks. Age-matched wild-type mice were used as control group. Renal protection of EA was evaluated by mouse urine production, water consumption, renal index and tubules dilation. Two-photon microscope imaging was applied to visualize renal microvascular blood flow in vivo. Immunostaining and western blot analysis were used to detect the glomerular alternations and inflammatory signaling. EA significantly attenuated renal dysfunction in db/db mice. The protective effect of EA on renal microvascular recovery was observed both in function and structure analysis. Firstly, EA restored the renal microvascular blood flow in db/db mice. Then, glomerular hypertrophy and glomerular barrier destruction were suppressed after EA, as respectively demonstrated by the reduction of glomerular dilation, Collagen Ⅳ and Claudin-1 deposits. In mechanism, EA suppressed the diabetes-induced inflammatory response in renal microvessels, presenting as the downregulation of inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α), intercellular cell adhesion molecule-1 (ICAM-1) activation, and macrophage infiltration after EA treatment. These findings indicated the benefits of EA against renal microvascular impairment and DKD progression, which was associated with the action of anti-inflammation, and supported EA as a promising modality for DKD management.