Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway

Yan-fang Xu; Shi-wei Ruan; Jiu-mao Lin; zheng Zhang

doi:10.1007/s11655-015-2078-5

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Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway

Updated：2021-08-27

- Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway
- Chinese Journal of Integrative Medicine Vol. 21, Issue 12, Pages: 928-937(2015)
- Affiliations：
  
  1. Department of Nephrology, The First Affiliated Hospital, Fujian Medical University,Fuzhou,China
  2. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine,Fuzhou,China
  3. People Hospital Affiliated to Fujian University of Traditional Chinese Medicine,Fuzhou,China
- Author bio：
- Funds：
- DOI：10.1007/s11655-015-2078-5
  CLC：
- Published：2015，
  
  Published Online：9 May 2015，
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Xu, Yf., Ruan, Sw., Lin, Jm. et al. Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway., Chin. J. Integr. Med. 21, 928–937 (2015). https://doi.org/10.1007/s11655-015-2078-5

Yan-fang Xu, Shi-wei Ruan, Jiu-mao Lin, et al. Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway. [J]. Chinese Journal of Integrative Medicine 21(12):928-937(2015)
Xu, Yf., Ruan, Sw., Lin, Jm. et al. Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway., Chin. J. Integr. Med. 21, 928–937 (2015). https://doi.org/10.1007/s11655-015-2078-5 DOI：

Yan-fang Xu, Shi-wei Ruan, Jiu-mao Lin, et al. Yishen Jiangzhuo Granules (益肾降浊冲剂) affect tubulointerstitial fibrosis via a mitochondrion-mediated apoptotic pathway. [J]. Chinese Journal of Integrative Medicine 21(12):928-937(2015) DOI： 10.1007/s11655-015-2078-5.

摘要

To investigate the effect of Yishen Jiangzhuo Granules (益肾降浊冲剂

YSJZG) on mitochondrial injury and regeneration and renal tubular epithelial cell apoptosis in chronic renal failure (CRF) rats and explore its mechanism from molecular pathology

gene

protein levels

and relative pathway. The CRF rat model was established using 5/6 nephrectomy. Sixty rats were randomly divided into six groups: sham-operation group

model (CRF) group

Niaoduqing Granules (尿毒清颗粒)-treated group [5 g/(kg.day)]

low-

moderate-

and high-dose [L-YSJZG

M-YSJZG

H-YSJZG at 3

and 9 g/(kg day)] YSJZG-treated group (n=10 each). The levels of serum creatinine (Scr)

blood urea nitrogen (BUN)

and 24-h urine protein were assessed after 10 weeks of treatment. The tubulointerstitial injury and collagen deposition were evaluated using periodic acid-schiff stain and Masson staining. Renal tubular epithelial cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay

mitochondrial injury was observed using an electron microscope

and superoxide dismutase (SOD)

glutathione (GSH) and malondialdehyde (MDA) levels were assessed using chromometry. Transforming growth factor-β1 (TGF-β1) expression was assessed using immunohistochemistry. The expressions of Bax

Bcl-2

peroxisome proliferator-activated receptor γ coactivator- 1α (PGC-1α)

mitochondrial transcription factor A (Tfam)

mitogen-activated protein kinases (MAPK) phosphorylation were evaluated by Western blot. YSJZG decreased the 24-h urine protein

BUN

Scr

remnant kidney weight-to-body weight ratio

renal tubular injury

deposition of collagen

and the apoptosis of renal tubular epithelial cells in a dose-dependent manner. YSJZG dose-dependently restored the number and structure of mitochondria and the expression of Tfam and PCG-1α

up-regulated the expression of Bcl-2

and inhibited the expression of Bax. YSJZG also dose-dependently inhibited TGF-β1 expression

increased SOD and GSH activity

decreased the MDA level

and inhibited p38MAPK and pERK1/2 phosphorylation (all P<0.01). YSJZG improved the renal function in rats with CRF and inhibited the progression of tubulointerstitial fibrosis by dose-dependently alleviating mitochondrial injury

restoring the expression of Tfam and PCG-1α

and inhibiting renal tubular epithelial cell apoptosis through inhibiting activation of reactive oxygen species-MAPK signaling.

Abstract

To investigate the effect of Yishen Jiangzhuo Granules (益肾降浊冲剂

YSJZG) on mitochondrial injury and regeneration and renal tubular epithelial cell apoptosis in chronic renal failure (CRF) rats and explore its mechanism from molecular pathology

gene

protein levels

and relative pathway. The CRF rat model was established using 5/6 nephrectomy. Sixty rats were randomly divided into six groups: sham-operation group

model (CRF) group

Niaoduqing Granules (尿毒清颗粒)-treated group [5 g/(kg.day)]

low-

moderate-

and high-dose [L-YSJZG

M-YSJZG

H-YSJZG at 3

and 9 g/(kg day)] YSJZG-treated group (n=10 each). The levels of serum creatinine (Scr)

blood urea nitrogen (BUN)

mitochondrial injury was observed using an electron microscope

and superoxide dismutase (SOD)

glutathione (GSH) and malondialdehyde (MDA) levels were assessed using chromometry. Transforming growth factor-β1 (TGF-β1) expression was assessed using immunohistochemistry. The expressions of Bax

Bcl-2

peroxisome proliferator-activated receptor γ coactivator- 1α (PGC-1α)

mitochondrial transcription factor A (Tfam)

mitogen-activated protein kinases (MAPK) phosphorylation were evaluated by Western blot. YSJZG decreased the 24-h urine protein

BUN

Scr

remnant kidney weight-to-body weight ratio

renal tubular injury

deposition of collagen

and the apoptosis of renal tubular epithelial cells in a dose-dependent manner. YSJZG dose-dependently restored the number and structure of mitochondria and the expression of Tfam and PCG-1α

up-regulated the expression of Bcl-2

and inhibited the expression of Bax. YSJZG also dose-dependently inhibited TGF-β1 expression

increased SOD and GSH activity

decreased the MDA level

restoring the expression of Tfam and PCG-1α

and inhibiting renal tubular epithelial cell apoptosis through inhibiting activation of reactive oxygen species-MAPK signaling.

关键词

Yishen Jiangzhuo Granulestubulointerstitial fibrosisapoptosismitochondriaoxidative stressmitogen-activated protein kinase signalingChinese Medicine

Keywords

Yishen Jiangzhuo Granulestubulointerstitial fibrosisapoptosismitochondriaoxidative stressmitogen-activated protein kinase signalingChinese Medicine

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Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine

Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine

Shanghai Key Laboratory of Complex Prescription

Chinese Medicine Hospital of Shanxi Province

Fujian Academy of Integrative Medicine

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