中药药理与临床2025，Vol.41Issue(4)：9-14,6.
加减补阳还五汤通过激活自噬促进Nrf2核转移改善糖尿病肾病足细胞损伤
Modified Buyang Huanwu(补阳还五)Decoction Ameliorates Podocyte Injury in Diabetic Kidney Disease by Activating Autophagy to Promote Nuclear Translocation of Nrf2
摘要
Abstract
Objective:To investigate whether modified Buyang Huanwu(补阳还五)Decoction can ameliorate podocyte injury in the mouse model of diabetic kidney disease(DKD)by activating autophagy to promote the nuclear translocation of nuclear factor-erythroid 2-related factor 2(Nrf2).Methods:A total of 24 db/db mice of 11-12 weeks old were selected.After one week of adaptive feeding and positive urinary protein monitoring,mice were randomized into model,modified Buyang Huanwu Decoction(16 g/kg),and rapamycin-treha-lose groups,while 8 db/m mice were included in the control group.Each group contained 8 mice.After 8 weeks of administration,the levels of fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),superoxide dismutase(SOD),malondialdehyde(MDA),glutathi-one peroxidase(GSH-PX),blood urea nitrogen(BUN),serum creatinine(Scr),kidney injury molecule-1(KIM-1),and microalbuminuria(mALB)were measured.The kidney tissue was stained with hematoxylin-eosin to reveal the pathological changes.The mRNA levels of wilms tumor 1 protein(Wt1),nephrin,and podocin were determined by real-time PCR.Western blotting was employed to assess the protein levels of P62/SQSTM1,Beclin1,microtubule-associated protein 1 light chain 3B(LC3-II),lysosomal associated membrane protein 1(LAMP1),Nrf2,Kelch-like ECH-associated protein 1(Keap1),quinone oxidoreductase 1(NQO1),and hemeoxygenase 1(HO-1)in the kidney tissue of mice.Immunofluorescence was utilized to identify the nuclear translocation of Nrf2.Results:Compared with the control group,the model group showed pathological injury in kidneys,elevated serum levels of FBG,TC,TG,MDA,BUN,Scr,KIM-1,and mALB,lowered levels of SOD and GSH-PX(P<0.01).Moreover,the model group presented increased expression of P62,decreased expression of LC3-II,Beclin1,and LAMP1(P<0.01),down-regulated mRNA levels of Wt1,nephrin,and podocin(P<0.01),and activated Nrf2-Keap1 pathway in the renal tis-sue(P<0.01).Compared with the model group,modified Buyang Huanwu Decoction alleviated the pathological injury in the renal tissue(P<0.01),lowered the serum levels of TC,TG,MDA,BUN,Scr,KIM-1,and mALB(P<0.01),elevated the levels of SOD and GSH-PX(P<0.01).Additionally,the treatment decreased the expression of P62,increased the expression of LC3-II,Beclin1,and LAMP1(P<0.01),re-stored the mRNA levels of Wt1,nephrin,and podocin,and activated the Nrf2-Keap1 pathway in the renal tissue(P<0.01).Conclusion:Mod-ified Buyang Huanwu Decoction can activate renal cell autophagy,dredge the autophagy pathway,promote the nuclear translocation of Nrf2,in-hibit oxidative stress,protect podocytes,and reduce urinary protein excretion,thereby ameliorating the renal injury in DKD.关键词
加减补阳还五汤/糖尿病肾脏疾病/自噬-溶酶体通路/核因子E2 相关因子 2-Kelch样ECH关联蛋白 1 通路/足细胞Key words
Modified Buyang Huanwu(补阳还五)Decoction/Diabetic kidney disease/Autophagy-lysosomal pathway/Nuclear factor-ery-throid 2-related factor 2(Nrf2)-Kelch-like ECH-associated protein 1(Keap1)pathway/Podocyte引用本文复制引用
杨帆,张晓云,娄菲菲,马赟,黄家安,刘利飞,赵炳武,王月华..加减补阳还五汤通过激活自噬促进Nrf2核转移改善糖尿病肾病足细胞损伤[J].中药药理与临床,2025,41(4):9-14,6.基金项目
河北省自然科学基金项目(编号:H2022423320、H2022423342) （编号:H2022423320、H2022423342）
河北省中医药管理局科研计划项目(编号:2023119、2024102) （编号:2023119、2024102）
河北省卫健委医学科学研究课题计划基金资助项目(编号:20230213) （编号:20230213）
河北中医药大学燕赵医学研究基金资助项目(编号:YZSY2023003). （编号:YZSY2023003）
