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Published on: December 4, 2010
Chronic allograft nephropathy in rats is improved by the intervention of rhein
1Department of Urology, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, China. nn77315@sohu.com
Aim:
In this study, we investigated the therapeutic efficacy and potential mechanisms of rhein to mitigate chronic allograft nephropathy (CAN) in rats.
Materials And Methods:
Fisher rat donors and Lewis rat recipients were used to establish the CAN model. Thirty rats with transplanted kidneys were randomly divided into two groups: 16 untreated and 14 rhein = treated rats. Five Lewis rat controls underwent removal of their right kidneys. The Intervention group was administered rhein oral solution (100 mg kg(-1) d(-1)) by gavage after transplantation. The untreated and control groups were given 0.5% sodium carboxymethyl cellulose. Blood and urine samples were collected at 4, 8, and 16 weeks to examine renal function and total urine protein. Half of the rats in each group were sacrifice at 8 or 16 weeks to examine renal pathology. Immunohistochemical examination and real-time polymerase chain reaction of renal tissues were performed to detect expressions of transforming growth-β1(TGF-β1), hepatic growth factor (HGF), bone morphogenetic protein 7 (BMP7), frobronectin, and collgen IV.
Results:
Rhein improved renal function and significantly reduced renal fibrosis and interstitial inflammation. The levels of BMP7 and HGF were significantly elevated in the renal tissues of the rhein intervention group. In the meantime, fibronectin and collagen IV were decreased in the extracellular matrix. The expression of TGF-β1 was similar between these two groups.
Conclusion:
Rhein improved renal function and reduced renal fibrosis and interstitial inflammation by inducing production of HGF and BMP7.
Insights
Rhein treatment improved kidney function and reduced scarring in a rat model of chronic allograft nephropathy (CAN). This therapeutic effect was linked to increased levels of hepatic growth factor (HGF) and bone morphogenetic protein 7 (BMP7).
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Chronic allograft nephropathy (CAN) is a major cause of kidney transplant failure.
- Identifying novel therapeutic strategies to mitigate CAN is crucial for improving long-term transplant outcomes.
Purpose of the Study:
- To evaluate the therapeutic efficacy of rhein in a rat model of CAN.
- To investigate the underlying mechanisms by which rhein exerts its effects on renal allografts.
Main Methods:
- A rat model of CAN was established using Fisher and Lewis rats.
- Rats were treated with rhein (100 mg/kg/day) or a control solution post-transplantation.
- Renal function, urine protein, and renal pathology were assessed. Gene and protein expression of TGF-β1, HGF, BMP7, fibronectin, and collagen IV were analyzed.
Main Results:
- Rhein treatment significantly improved renal function and reduced renal fibrosis and interstitial inflammation.
- Rhein administration led to increased levels of hepatic growth factor (HGF) and bone morphogenetic protein 7 (BMP7) in renal tissues.
- Expressions of fibronectin and collagen IV in the extracellular matrix were decreased, while TGF-β1 expression remained similar between groups.
Conclusions:
- Rhein demonstrates significant therapeutic efficacy in mitigating chronic allograft nephropathy in rats.
- The protective effects of rhein are mediated through the induction of HGF and BMP7, leading to reduced renal fibrosis and inflammation.
