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Effect and mechanism of crocin on renal fibrosis in rats with diabetic nephropathy
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DOI   10.11656/j.issn.1672-1519.2023.04.18
Key Words   crocin;diabetic nephropathy;fibrosis;collagen;Klotho/TGF-β/Smad signaling pathway
Author NameAffiliation
ZHOU Jing Kailuan General Hospital, Tangshan 063000, China 
GUO Yangyang Fourth People's Hospital of Langfang City, Langfang 065700, China 
LU Chunhong Kailuan General Hospital, Tangshan 063000, China 
HUANG Jinjie Kailuan General Hospital, Tangshan 063000, China 
WANG Dan Kailuan General Hospital, Tangshan 063000, China 
Abstract
    [Objective] To investigate the effect and mechanism of crocin on renal fibrosis in diabetic nephropathy (DN) rats. [Methods] The DN rat models were prepared by feeding high-fat diet for 4 weeks and intraperitoneal injection of streptozotocin. The 50 rat models were randomly divided into model group (saline), metformin (500 mg/kg) group and crocin low, medium and high dose groups (25, 50, 100 mg/kg) group;and the normal control group (saline) was set up;the drugs were given once a day for 12 weeks. The body weight, fasting blood sugar level and the renal function index were detected;the renal histopathology and fibrosis were examined by Hematoxylin-Yinhong (HE) staining and Masson staining;the expression of Klotho, transforming growth factor-β1 (TGF-β1), phosphorylated Smad2 (p-Smad2) were detected by Western blot method. [Results] Compared with model group, the body weight of the rats in the crocin medium-, high-dose group and metformin group was increased, the fasting blood glucose levels, 24 h urine protein (UPro), the levels of urea nitrogen (BUN), creatinine (SCr) in serum were decreased;the histopathology such as glomerulus enlargement, renal interstitial inflammatory cell infiltration, mesangial and basement membrane hyperplasia and glomerular, renal interstitial fibrosis were significantly improved, and the collagen volume fraction (CVF) was reduced;the expression of Klotho was up-regulated and the expression of TGF-β1, p-Smad2 were down-regulated, all of the difference were significant (P<0.05 or P<0.01). Compared with metformin group, the body weight of rats in the crocin high-dose group was increased;the UPro and the levels of BUN, SCr in serum were decreased;the CVF was decreased;the expression of Klotho was up-regulated and the expression of TGF-β1, p-Smad2 were down-regulated, all of the difference were significant (P<0.05 or P<0.01). [Conclusion] Crocin has inhibitory effect on renal fibrosis in DN rats, which may be related to the inhibition of Klotho/TGF-β/Smad signaling pathway.

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