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Huayu Tongluo Chinese medicines activating autophagy by regulating AMPK/mTOR pathway to improve renal injury in diabetic nephropathy rats
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DOI   10.11656/j.issn.1672-1519.2025.05.17
Key Words   diabetes nephropathy;Huayu Tongluo Chinese medicine;autophagy;AMPK/mTOR signaling pathway
Author NameAffiliationE-mail
ZHANG Xiqiao Graduate School, Hebei University of Chinese Medicine, Shijiazhuang 050091, China  
ZHANG Xueqin Graduate School, Hebei University of Chinese Medicine, Shijiazhuang 050091, China  
MA Yun The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang 050000, China  
LIU Ziyue Graduate School, Hebei University of Chinese Medicine, Shijiazhuang 050091, China  
LI Liang Graduate School, Hebei University of Chinese Medicine, Shijiazhuang 050091, China  
CHEN Zhiqiang Graduate School, Hebei University of Chinese Medicine, Shijiazhuang 050091, China
The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang 050000, China
Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Liver and Kidney Disease Research, Shijiazhuang 050091, China
Hebei Technology Innovation Center of Traditional Chinese Medicine Spleen and Kideney Diseaes, Shijiazhuang 050000, China 
chenzhqiang2011@163.com 
Abstract
    [Objective] To investigate the therapeutic effect of the traditional Chinese medicine of resolving blood stasis and promoting collaterals on the kidneys of rats with diabetic nephropathy(DN) and its mechanism of action. [Methods] The rats were randomly divided into 30 rats in the modeling group and 10 rats in the control group. The modeling group had the right kidney removed + streptozotocin(1%,40 mg/kg) injected intraperitoneally,and the modeled rats were randomly divided into 10 rats in the model group,10 rats in the group of traditional Chinese medicines for resolving blood stasis and clearing the channels and 10 rats in the group of Irbesartan. After 12 weeks of drug administration,the levels of glycated albumin(GA),cholesterol(TC),triacylglycerol(TG),urea nitrogen(BUN),creatinine(Scr),and 24-hour urinary protein(24 h UTP) were measured;the pathological and morphological changes of the renal tissues of the rats were observed by light microscopy;the levels of SQSTM1/p62,human microtubule-associated protein light chain(LC3B-Ⅱ),human microtubule-associated protein light chain(LC3B-Ⅱ),and human microtubule-associated protein light chain(LC3B-Ⅱ) were detected by immunoblotting. 3B-Ⅱ(LC3B-Ⅱ)/human microtubule-associated protein light chain 3B-Ⅰ(LC3B-Ⅰ),adenylate-activated protein kinase(AMPK),phosphorylated adenylate-activated protein kinase(p-AMPK),mammalian target of rapamycin(mTOR),and phosphorylated mammalian target of rapamycin(p-mTOR). [Results] Compared with the control group,serum GA,TC,TG,BUN and 24 h UTP levels were significantly increased in the model group,renal tissue showed obvious pathological damage,renal tissue p-AMPK/AMPK,LC3B-Ⅱ/LC3B-Ⅰ expression was decreased,and p-mTOR/mTOR,p62 expression was elevated(P<0.05 or P<0.01);compared with the model group,DN rats had decreased serum TC,TG,BUN and 24 h UTP levels and improved renal tissue pathological damage after intervention with the traditional Chinese medicine of resolving blood stasis and promoting circulation. Compared with the model group,after the intervention of traditional Chinese medicine,the serum TC,TG,BUN and 24 h UTP levels of DN rats were reduced,the pathological damage of renal tissue was improved,and the expression of LC3B-Ⅱ/LC3B-Ⅰ,p-AMPK/AMPK in renal tissue was elevated,and the expression of p62,p-mTOR/mTOR was reduced(P<0.05 or P<0.01). [Conclusion] Resolving blood stasis and opening up the channels of Chinese medicine can reduce renal injury and delay the decline of renal function,and its potential mechanism of action may be related to the regulation of autophagy mediated by the AMPK/mTOR signaling pathway.

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