Tissue & cell · 2026
Acupuncture inhibits ferroptosis and epithelial-mesenchymal transition to attenuate proteinuria in diabetic kidney disease.
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Zhang Peng, Song Amiao, Tian Yun, Shao Di
Аннотация
BACKGROUND: The pathogenesis of diabetic kidney disease (DKD) is closely related to ferroptosis (FeP) and epithelial-mesenchymal transition (EMT). Whether acupuncture alleviates proteinuria in DKD by inhibiting the above pathways remains unclear.
OBJECTIVE: The role and mechanism of acupuncture in reducing proteinuria in DKD rats by regulating the FeP and EMT pathways were investigated.
METHODS: Forty-eight male SD rats were randomly divided into 8 groups (n = 6 per group): normal control group (NC group), model control group (MC group), acupuncture group (CG group), sham acupuncture control group (Sham-CG group), positive drug control group (Drug-CG group), ferroptosis inhibitor control group (FeP-Inh-CG group), EMT activator control group (EMT-Act-CG group), and EMT inhibitor control group (EMT-Inh-CG group). A DKD model was established. In the CG group, acupuncture was performed at the acupoints "Zusanli" (ST36), "Sanyinjiao" (SP6), and "Shenshu" (BL23) for 6 weeks. Renal function indicators, urinary kidney injury markers, FeP-related proteins, and EMT markers were detected in each group RESULTS: Compared with the MC group, serum creatinine (Scr), blood urea nitrogen (BUN), and 24-hour urinary protein (24 h Upro) levels were significantly decreased in the CG group; levels of urinary microalbumin/creatinine (mALB/Cr), β2-microglobulin (β2-MG), and kidney injury molecule-1 (KIM-1) were reduced. Western blot showed that the protein expression of GPX4 and SLC7A11 was upregulated, while ACSL4 expression was downregulated in the CG group. qPCR results showed that E-cadherin mRNA expression was increased, and N-cadherin and α-SMA mRNA expressions were decreased in the CG group. Furthermore, the improvement effects of the CG group on indicators such as 24 h Upro and mALB/Cr were superior to those of the Drug-CG group and the FeP-Inh-CG group. 24 h Upro was negatively correlated with GPX4, SLC7A11, and E-cadherin (r = -0.756 to -0.803) and positively correlated with ACSL4, N-cadherin, and α-SMA (r = 0.776-0.834) (all P < 0.001).
CONCLUSION: Acupuncture can alleviate oxidative stress injury, improve renal function, and reduce proteinuria by inhibiting renal cell FeP and blocking the EMT process. The mechanism is related to the regulation of GPX4/SLC7A11/ACSL4 and E-cadherin/N-cadherin/α-SMA expression, and this therapeutic effect has the advantages of acupoint specificity and multi-target action.
OBJECTIVE: The role and mechanism of acupuncture in reducing proteinuria in DKD rats by regulating the FeP and EMT pathways were investigated.
METHODS: Forty-eight male SD rats were randomly divided into 8 groups (n = 6 per group): normal control group (NC group), model control group (MC group), acupuncture group (CG group), sham acupuncture control group (Sham-CG group), positive drug control group (Drug-CG group), ferroptosis inhibitor control group (FeP-Inh-CG group), EMT activator control group (EMT-Act-CG group), and EMT inhibitor control group (EMT-Inh-CG group). A DKD model was established. In the CG group, acupuncture was performed at the acupoints "Zusanli" (ST36), "Sanyinjiao" (SP6), and "Shenshu" (BL23) for 6 weeks. Renal function indicators, urinary kidney injury markers, FeP-related proteins, and EMT markers were detected in each group RESULTS: Compared with the MC group, serum creatinine (Scr), blood urea nitrogen (BUN), and 24-hour urinary protein (24 h Upro) levels were significantly decreased in the CG group; levels of urinary microalbumin/creatinine (mALB/Cr), β2-microglobulin (β2-MG), and kidney injury molecule-1 (KIM-1) were reduced. Western blot showed that the protein expression of GPX4 and SLC7A11 was upregulated, while ACSL4 expression was downregulated in the CG group. qPCR results showed that E-cadherin mRNA expression was increased, and N-cadherin and α-SMA mRNA expressions were decreased in the CG group. Furthermore, the improvement effects of the CG group on indicators such as 24 h Upro and mALB/Cr were superior to those of the Drug-CG group and the FeP-Inh-CG group. 24 h Upro was negatively correlated with GPX4, SLC7A11, and E-cadherin (r = -0.756 to -0.803) and positively correlated with ACSL4, N-cadherin, and α-SMA (r = 0.776-0.834) (all P < 0.001).
CONCLUSION: Acupuncture can alleviate oxidative stress injury, improve renal function, and reduce proteinuria by inhibiting renal cell FeP and blocking the EMT process. The mechanism is related to the regulation of GPX4/SLC7A11/ACSL4 and E-cadherin/N-cadherin/α-SMA expression, and this therapeutic effect has the advantages of acupoint specificity and multi-target action.