Electroacupuncture ameliorates diabetic renal injury by regulating the AMPK-autophagy signaling pathway

Objective(s): Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) and the leading cause of end-stage renal disease worldwide. Despite evidence supporting the renoprotective effects of electroacupuncture (EA), the underpinning molecular mechanisms require further investigation. This study was designed to evaluate the therapeutic efficacy of EA in mice with DN and to elucidate its potential mechanisms of action.Materials and Methods: A DN model was established in male C۵۷BL/۶ mice by streptozotocin (STZ) injection and validated. Mice were randomly allocated into four groups: control, normal+electroacupuncture (EA), DN, and DN+EA. EA was applied at Yanglingquan and Zusanli acupoints in the treatment groups. Renal histology and ultrastructure were examined. AMPK and downstream autophagy-related molecule expression were analyzed by qRT-PCR and Western blot.Results: Renal tissues from DN mice exhibited suppressed autophagy, marked by decreased microtubule-associated protein ۱ light chain ۳-II (LC۳-II) and increased Sequestosome-۱ (p۶۲) expression, along with reduced phosphorylation of AMP-activated protein kinase (AMPK) and Unc-۵۱ Like Autophagy Activating Kinase ۱(ULK۱) and increased Phosphorylated mammalian target of rapamycin (p-mTOR) levels after ۸ weeks, indicating impaired autophagy and renal injury. EA treatment reversed these alterations by enhancing AMPK and ULK۱ phosphorylation, restoring autophagy, and mitigating renal damage.Conclusion: The AMPK signaling pathway represents a novel therapeutic target for DN. Our data indicate that EA facilitates renal protection by activating AMPK/ULK۱-mediated autophagy, implicating EA as a viable strategy for targeting this pathway.

کلیدواژه ها:

AMP-activated protein- kinase ، Autophagy ، Diabetic nephropathy ، Electroacupuncture ، ULK۱