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Abstract: FR-PO156

Nicorandil Plays a Protective Role Against Renal Fibrosis in Unilateral Ureteral Ligation Models via Reducing TGF-β1/Collagen Expression and Improving Energy Metabolism

Session Information

Category: Glomerular Diseases

  • 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix


  • Chen, Yingying, Department of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, China
  • Chen, Lan, Department of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, China
  • Ling, Yisheng, Department of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, China
  • Guan, Tianjun, Department of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, China

As one of most important metabolic sensors, ATP-sensitive potassium channels (KATP) could regulate cellular activity to meet energetic demands. It has also been demonstrated that KATP plays a protective role on several ischemia-associated diseases. However, there are few studies to clarify whether KATP opener could directly improve renal function or renal fibrosis in unilateral ureteral ligation (UUO) models.This experimental study was designed to clarify the effect and mechanism of nicorandil (a KATP opener) on renal dysfunction, extracellular matrix expression and ATP generation in mice renal fibrosis model caused by unilateral ureteral ligation.


Mice UUO models were developed and observed at 7th and 14th day after operation. There were three groups in our study: sham-operation (n=12), UUO (n=12), UUO+nicorandil (n=12). In nicorandil treatment group, nicorandil was injected intraperitoneally daily (20mg/kg/d) for 12 days from the third day of UUO operation. Renal function and ATP synthesis (using an ATP assay kit, FLAA, Sigma, USA) were detected at 7th and 14th day after operation. Masson trichrome staining was performed to analyze collagen generation. TGF-β1 and Smad3 were detected by Western blot.


Compared with sham-operation group, UUO groups had a significantly higher serum level of creatinine (7th day: 55.9±4.8 vs. 35.7±3.2μmol/L, P<0.01; 14th day: 82.0±7.8 vs. 35.2±6.2μmol/L, P<0.01). Nicorandil treatment not only reduced serum creatinine level (7th day: 45.7±3.6 vs. 55.9±4.8μmol/L, P<0.05; 14th day 64.3±5.5 vs. 82.0±7.8μmol/L, P<0.01), but also reduced collagen volume fraction (7th day: 10.5±2.8% vs. 17.6±3.8%, P<0.01; 14th day: 16.4±3.8% vs. 34.2±5.2%, P<0.01). We also found that TGF-β1 and Smad3 expression were significantly reduced in nicorandil treatment group. Furthermore, renal ATP synthase was also improved significantly (sham operation group: 8.55±2.74 nmol/L; UUO group: 2.92±1.96 nmol/L; UUO+nicorandil group: 4.88±1.48 nmol/L, P<0.05).


KATP opener nicorandil protected against UUO-induced renal fibrosis, which were associated with TGF-β1/collagen expression and energy metabolism recovery.


  • Government Support - Non-U.S.