从"虚损痨瘵,燮理气阴"探讨糖尿病肾病铁死亡病机及防治思路OA

Based on the theory of"treating consumptive deficiency by harmonizing qi and yin",this paper explores ferroptosis-centered pathological mechanisms and corresponding prevention and treatment strategies for diabetic kidney disease(DKD).Deficiency of the spleen and kidney serves as the root cause,while damp-heat,phlegm-stasis,and turbidity-toxin represent the manifestations.Together,these factors disrupt iron homeostasis,characterized by downregulation of solute carrier family 7 member 11(SLC7A11,xCT)and glutathione peroxidase 4(GPX4)and upregulation of long-chain acyl-CoA synthetase family member 4(ACSL4).These imbalance triggers lipid peroxidation and ferroptosis,damaging renal tubular epithelial cells and podocytes.Subsequently,through damage-associated molecular patterns(DAMPs),transforming growth factor-β(TGF-β)/Smad,and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)signaling pathways,it promotes fibroblast activation and collagen deposition,ultimately leading to renal fibrosis.Guided by the concept of"preventing a disease before it arises",a three-tier prevention and treatment strategy is proposed:in the early stage,strengthening the spleen,replenishing qi,nourishing yin,and transforming dampness,combined with antioxidant and anti-ferroptotic interventions,to delay the onset of microalbuminuria;during the moderate stage,clearing heat and removing toxins,circulating blood and unblocking collaterals,while synergistically modulating the nuclear factor E2-related factor 2(Nrf2)/GPX4,ACSL4,as well as the TGF-β/Smad axis,to suppress inflammation and fibrosis amplification;in the late stage,reinforcing healthy qi,consolidating the root,warming yang and disinhibiting water,while integrating toxin removing,collateral unblocking,and renal protection,to alleviate symptoms and improve prognosis.