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Journal of Traditional Chinese Medicine >

2024 , Vol. 44 >Issue 5: 934 - 943

DOI: https://doi.org/10.19852/j.cnki.jtcm.20231231.001

Effect of phosphatase and tensin homolog-induced putative kinase 1/ E3 ubiquitin ligase Parkin mediated mitochondrial autophagy on chronic kidney disease myocardial injury and the intervention mechanism of Shenshuai recipe (肾衰方)

  • Gedi ZHANG ,
  • Gengxin LIU ,
  • Min GUO ,
  • Fuli LUO ,
  • Ziyou YAN ,
  • Wei GE
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  • 1 School of Graduate, Jiangxi University of Chinese Medicine, Nanchang 330000, China
    2 Department of Nephrology, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang 330000, China
    3 Department of Anorectal, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang 330000, China

Received date: 2023-06-22

  Accepted date: 2023-10-10

  Online published: 2023-12-31

Supported by

Effect of Phosphatase and Tensin Homolog-induced Putative Kinase 1/Parkin Mediated Mitochondrial Autophagy on Myocardial Injury in Chronic Kidney Disease and the Intervention Mechanism of Shenshuai Recipe(81960843);Training Plan for Young and Middle-aged Key Talents Project of Traditional Chinese Medicine of Jiangxi Province (No. [2022] 7)

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Abstract

OBJECTIVE: To study whether Shenshuai recipe (肾衰方, SSR) can play a protective role on chronic kidney disease myocardial injury model through phosphatase and tensin homolog-induced putative kinase 1 (PINK1)/E3 ubiquitin ligase Parkin (Parkin) mitochondrial autophagy pathway.

METHODS: Forty-eight nephrectomized rats were randomly divided into six groups: sham-operated group, model group, Benazepril group, low, medium and high-dose groups of SSR. The rats were given the cor-responding intervention for six weeks, then were sacrificed. Serum was examined by enzyme linked immunosorbent assay (ELISA). Cardiac ultrasound was used to detect cardiac function in 5/6 nephrectomized rats. Myocardial tissue was examined by light and electron microscopy; PINK1, Parkin, microtubule-associated protein1 light chain 3 II (LC3B), sequestosome 1 (P62), BECN1 (Beclin-1) and dynamin-related protein 1 (Drp-1) were measured by real time polymerase chain reaction (RT-PCR), Western blot (WB) and immunohistochemistry (IHC).

RESULTS: The expression levels of blood urea nitrogen (BUN) and creatinine (SCr) in the model group were significantly higher than those in the sham-operated group, indicating that modeling was successful. SSR can protect myocardium by reducing the relative expression of creatine kinase myocardial isoenzyme and hypersensitivity cardiac troponin I (P<0.05). SSR can improve cardiac function in rats after ultrasound testing. SSR can improve the pathological manifestations of myocardial tissue after Masson staining. SSR can increase the number of autophagosomes and autophagiclysosomes in 5/6 nephrectomized rats (P<0.05). Determined by RT-PCR, WB and IHC, SSR can increase the relative expression of PINK1, Parkin, and LC3B (P<0.05), and decrease the relative expression of P62, Beclin-1 and Drp-1 (P<0.05).

CONCLUSIONS: The PINK1/Parkin mitochondrial autophagy pathway in myocardial tissues in 5/6 nephrectomy CKD myocardial injury rats was inhibited. SSR can activate PINK1/Parkin mitochondrial autophagy to enhance mitochondrial autophagy, and play a protective role in myocardial tissues.

Key words： renal insufficiency, chronic; PTEN phosphohydrolase; ubiquitin-protein ligases; myocardial injury; mitochondrial autophagy; Shenshuai recipe

Cite this article

Gedi ZHANG , Gengxin LIU , Min GUO , Fuli LUO , Ziyou YAN , Wei GE . Effect of phosphatase and tensin homolog-induced putative kinase 1/ E3 ubiquitin ligase Parkin mediated mitochondrial autophagy on chronic kidney disease myocardial injury and the intervention mechanism of Shenshuai recipe (肾衰方)[J]. Journal of Traditional Chinese Medicine, 2024 , 44(5) : 934 -943 . DOI: 10.19852/j.cnki.jtcm.20231231.001

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