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Yishen Jiangzhuo Granules affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway

Yan-fang Xu1, Shi-wei Ruan2,3, Jiu-mao Lin2

  • 1Department of Nephrology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China. xuyanfang99@hotmail.com.

Chinese Journal of Integrative Medicine
|May 10, 2015
PubMed
Abstract

Insights

Yishen Jiangzhuo Granules (YSJZG) treatment improved renal function in chronic renal failure (CRF) rats. YSJZG alleviated mitochondrial injury and renal tubular cell apoptosis, inhibiting tubulointerstitial fibrosis progression.

Area of Science:

  • Nephrology
  • Pharmacology
  • Molecular Biology

Background:

  • Chronic renal failure (CRF) is characterized by progressive kidney damage, often involving mitochondrial dysfunction and tubular cell apoptosis.
  • Understanding the molecular mechanisms underlying CRF progression is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the therapeutic effects of Yishen Jiangzhuo Granules (YSJZG) on mitochondrial injury and renal tubular epithelial cell apoptosis in a rat model of CRF.
  • To elucidate the underlying molecular mechanisms, including gene and protein expression, and signaling pathways involved.

Main Methods:

  • A 5/6 nephrectomy rat model of CRF was established and treated with varying doses of YSJZG or a control drug for 10 weeks.
  • Evaluations included serum markers (creatinine, BUN, urine protein), histological analysis (tubulointerstitial injury, collagen deposition), apoptosis assays, mitochondrial morphology assessment, and Western blot analysis for key proteins (Bax, Bcl-2, PGC-1α, Tfam, MAPK).

Main Results:

  • YSJZG significantly reduced markers of renal damage (urine protein, BUN, Scr) and tubulointerstitial fibrosis in a dose-dependent manner.
  • Treatment with YSJZG restored mitochondrial structure and function, upregulated protective proteins (Bcl-2, Tfam, PGC-1α), and downregulated pro-apoptotic proteins (Bax).
  • YSJZG inhibited TGF-β1 expression, reduced oxidative stress markers (MDA), and decreased MAPK phosphorylation (p38MAPK, pERK1/2).

Conclusions:

  • Yishen Jiangzhuo Granules demonstrate significant renoprotective effects in CRF rats.
  • YSJZG ameliorates renal dysfunction and inhibits tubulointerstitial fibrosis by alleviating mitochondrial injury and apoptosis.
  • The mechanism involves restoring mitochondrial biogenesis markers and inhibiting the reactive oxygen species-MAPK signaling pathway.
Keywords:
Chinese medicineYishen Jiangzhuo Granulesapoptosismitochondriamitogen-activated protein kinase signalingoxidative stresstubulointerstitial fibrosis

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