Diabetic kidney disease (DKD) has been a common microvascular complication in diabetes mellitus, and the predominant risk of end-stage renal disease and mortality in type 2 diabetes mellitus (T2DM) [1,2]. DKD was featured with glomerular hypertrophy, mesangial matrix expansion, basement membrane thickness, podocyte detachment, and tubular dilation, then developing into glomerular fibrosis and tubulointerstitial fibrosis [3]. In treatment, pharmaceutical interventions to control blood glucose, cholesterol, and blood pressure are widely used, however, still far from the aims of preventing DKD progression [4,5]. It is urgent to develop more therapeutic modalities for DKD treatment. In China, manual acupuncture, electroacupuncture (EA) based on traditional Chinese medicine has been applied as an alternative modality in diabetes treatment and kidney modulation [6,7]. Combined with electrical stimulation to acupuncture needles, EA provides a more accurate and quantitatively controlled approach to acupuncture treatment [8]. Clinical studies have implicated the positive role of manal acupuncture and EA in attenuating renal injury [9], [10], [11]. These advantages of efficiency and low adverse effects endow manual acupuncture and EA with great potency in DKD therapy. However, the underlying mechanism mediating renal protection of acupuncture remains obscure.

Renal capillary, including glomerular capillary and peritubular capillary, is crucial for kidney homeostasis, but also the primary target vulnerable to diabetic pathology [12], [13], [14]. Significant loss of renal microvascular density and endothelial injury was observed both in diabetic mice and patients [15,16]. Renal microvascular impairment results in enhanced glomerular permeability, renal hypoperfusion, hypoxia, inflammation, macrophage infiltration and disorder of renal cellular metabolism, promoting the progression of renal fibrosis and renal failure [17]. Thus, besides renal tubular cells, protection of the renal capillaries in structure and function is necessary to block DKD progression [12,18]. Although hyperglycemia is considered as the primary factor leading to renal microvascular impairment, the microvascular protection from single anti-hyperglycemia treatment is limited [19,20]. Studies have demonstrated that inflammation plays a critical role in the onset and progression of renal microvascular injury [18,21]. Higher levels of proinflammatory cytokines have been found in DKD patients, which may occur even before the symptoms of renal dysfunction [22]. Exposure of proinflammatory cytokine activates endothelial cells and upregulates the endothelial adhesion molecules including intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These alternations subsequently enhance the leukocyte infiltration to the glomeruli and tubules and exaggerate the inflammatory injury in the kidney [16,23]. Therefore, anti-inflammation combined with glucose regulation might work better in renoprotection against DKD progression.

Thus, this study was designed to investigate the effect of EA on renal microvascular repair and renal protection in db/db diabetic mice, and dissected the working mechanism focusing on inflammatory modulation.