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Experimental Mechanism of Triptolide Delaying Glomerulosclerosis in Chronic Kidney Disease
Zhidan Deng1, Lijuan Chai2, Jingjing Wang1
1Department of Nephrology, The Fourth Hospital of Changzhou, 231002 Changzhou, Jiangsu, China.
Objective:
To explore the impact of Tripterygium wilfordii glycosides (TWG) on glomerulosclerosis within a rat model of chronic kidney disease (CKD), as well as the role of the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway in this mechanism.
Methods:
Twenty-four clean Sprague-Dawley rats were divided into Sham group (n = 8), model group (n = 8) and TWG group (n = 8). Adriamycin nephropathy (ADRN) rat model was established by jugular vein injection of adriamycin (ADR). TWG rats were given TWG 50 mg/kg intragastrically once a day for 6 weeks. After 10 weeks, the ratio of total cell number to glomerulus, extracellular matrix (ECM) and collagen (Coll) deposition, a-smooth muscle actin (a-SMA), type I collagen (Col1) expression, TGF-β1, p-Smad2/3mRNA expression and TGF-β1, p-Smad2/3 protein expression were compared in each group.
Results:
Masson staining revealed that in the model group, there was an increase in glomerular fibrosis, a heightened deposition of collagen fibers, and an expansion of interstitial spaces; Conversely, in the electroacupuncture group, the deposition of glomerular collagen fibers diminished. The intensity of a-SMA and ColI immunofluorescence staining in the kidney tissue of rats from the model group was markedly higher than that observed in the Sham group (p < 0.0001, < 0.0001 respectively). In contrast, the a-SMA and ColI immunofluorescence staining intensity in the TWG group was reduced compared to the model group (p = 0.009, 0.016 respectively). Furthermore, the expression levels of TGF-β1 and Smad3 messenger RNA (mRNA) in the kidney tissue of rats in the TWG group were lower than those in the model group (p = 0.013, 0.008, respectively), while the Smad7 mRNA was elevated compared to the model group (p = 0.019, 0.011, respectively). Additionally, the protein expression levels of TGF-β1 and p-Smad2/3 in the kidney tissue of rats in the TWG group were diminished compared to those in the model group (p < 0.0001, 0.006 respectively).
Conclusions:
TWG can improve glomerulosclerosis and delay its progression, which may be achieved by down-regulating TGF-β1/Smad signal pathway.
Insights
Tripterygium wilfordii glycosides (TWG) show promise in treating glomerulosclerosis in chronic kidney disease (CKD) rats. TWG treatment down-regulates the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway, improving kidney function.
Area of Science:
- Nephrology
- Pharmacology
- Molecular Biology
Background:
- Glomerulosclerosis is a hallmark of chronic kidney disease (CKD).
- The transforming growth factor-β1 (TGF-β1)/Smad signaling pathway is implicated in the pathogenesis of glomerulosclerosis.
- Novel therapeutic strategies targeting this pathway are needed for CKD treatment.
Purpose of the Study:
- To investigate the therapeutic effects of Tripterygium wilfordii glycosides (TWG) on glomerulosclerosis in a rat model of CKD.
- To elucidate the role of the TGF-β1/Smad signaling pathway in the protective mechanism of TWG.
Main Methods:
- An Adriamycin nephropathy (ADRN) rat model was established to induce CKD.
- Rats were divided into Sham, model, and TWG treatment groups.
- Histological analysis, immunofluorescence staining, and gene/protein expression analysis of key markers (e.g., a-SMA, ColI, TGF-β1, Smad proteins) were performed.
Main Results:
- ADRN rats exhibited significant glomerulosclerosis, collagen deposition, and increased a-SMA and ColI expression.
- TWG treatment significantly reduced glomerular fibrosis, collagen deposition, and a-SMA/ColI expression compared to the model group.
- TWG administration led to decreased expression of TGF-β1 and p-Smad2/3, and increased Smad7 expression at both mRNA and protein levels.
Conclusions:
- Tripterygium wilfordii glycosides (TWG) demonstrate a protective effect against glomerulosclerosis in a rat model of CKD.
- TWG exerts its renoprotective effects possibly by inhibiting the TGF-β1/Smad signaling pathway.
