Effects of stachydrine on podocyte injury in diabetic nephropathy rats by regulating the SDF-1/CXCR4 signaling pathway
ObjectiveTo investigate the effect of stachydrine （Sta） on podocyte injury in rats with diabetic nephropathy （DKD） by regulating the stromal cell derived factor-1（SDF-1）/chemokine receptor-4（CXCR4） signaling pathway.MethodsRats were randomly separated into the Control group， Model group， low-dose St...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | zho |
| Published: |
Editorial Department of Journal of Clinical Nephrology
2025-06-01
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| Series: | Linchuang shenzangbing zazhi |
| Subjects: | |
| Online Access: | http://www.lcszb.com/thesisDetails#10.3969/j.issn.1671-2390.2025.06.009 |
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| Summary: | ObjectiveTo investigate the effect of stachydrine （Sta） on podocyte injury in rats with diabetic nephropathy （DKD） by regulating the stromal cell derived factor-1（SDF-1）/chemokine receptor-4（CXCR4） signaling pathway.MethodsRats were randomly separated into the Control group， Model group， low-dose Stagroup （Sta-L）， high-dose Stagroup （Sta-H）， and Sta-H+AMD3100 （SDF-1/CXCR4 signaling pathway inhibitor） group. Fasting blood glucose （FBG）， urea nitrogen （BUN）， serum creatinine （Scr） and 24-hour urine protein （UP） levels were measured. Enzyme linked immunosorbent assay （ELISA） was used to detect serum levels of lactic dehydrogenase （LDH）， tumor necrosis factor （TNF-α）， tumor necrosis factor （IL-6） and interleukin-4 （IL-4）. Hematoxylin and eosin staining （H&E） was used to observe the pathological morphology of kidney tissue. Transmission electron microscopy （TEM） was used to observe the ultrastructure of glomerular podocytes. Western blot was used to detect the protein expressions of recombinant podocalyxin （PCX）， Nephrin， Desmin， cleaved cysteine protease-3 （cleaved caspase-3）， SDF-1 and CXCR4 in kidney tissue.ResultsCompared with the Control group， rats in the model group had greatly damaged kidney tissue， destroyed podocyte microstructure， significantly higher FBG （24.93±3.24 mmol/L <italic>vs</italic> 5.16±0.87 mmol/L）， BUN （16.23±1.81 mmol/L <italic>vs</italic> 5.64±0.92 mmol/L）， Scr（107.38±12.74 μmol/L <italic>vs</italic> 5.16±0.87 μmol/L）， UP（37.69±4.72 mg <italic>vs</italic> 6.51±1.18 mg）， serum LDH （9.48±1.51 U/L <italic>vs</italic> 2.09±0.37 U/L）， TNF-α （176.43±22.53 ng/L <italic>vs</italic> 43.79±5.84 ng/L）， IL-6 （134.76±17.83 ng/L <italic>vs</italic> 28.63±3.57 ng/L）， renal tissue injury score （2.80±0.24 <italic>vs</italic> 0.10±0.02）， and protein levels of Desmin （1.28±0.16 <italic>vs</italic> 0.36±0.05） and cleaved caspase-3 （0.78±0.10 <italic>vs</italic> 0.19±0.03）， but significantly lower serum IL-4 （21.37±3.61 ng/L <italic>vs</italic> 107.52±13.94 ng/L）， and protein levels of PCX （0.31±0.05 <italic>vs</italic> 1.17±0.14）， Nephrin （0.26±0.04 <italic>vs</italic> 1.04±0.13）， SDF-1 （0.31±0.05 <italic>vs</italic> 0.95±0.13） and CXCR4 （0.24±0.03 <italic>vs </italic>0.86±0.11） in kidney tissues （<italic>P</italic><0.05）. Compared with the Model group， rats in the Sta-L group and Sta-H group had greatly improved morphology of kidney tissue， reduced degree of podocyte microstructure damage， significantly lower FBG， BUN， Scr and UP levels， serum LDH， TNF-α， IL-6 levels， renal tissue injury score， and protein levels of Desmin and cleaved caspase-3， but significantly higher serum IL-4 level， and protein levels of PCX， Nephrin， SDF-1 and CXCR4 in kidney tissues increased （<italic>P</italic><0.05）. AMD3100 could attenuate the ameliorating effect of Sta on podocyte injury in DKD rats （<italic>P</italic><0.05）.ConclusionSta can reduce blood glucose and inflammation in DKD rats， and alleviate renal tissue and podocyte damage by activating the SDF-1/CXCR4 signaling pathway. |
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| ISSN: | 1671-2390 |