Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Protective effect of cilostazol on vascular injury in rats with acute ischemic stroke complicated with chronic renal failure

  • Ru Sun (Department of Neurology, the First People's Hospital of Huzhou, First affiliated Hospital of Huzhou University) ;
  • Qun Gu (Department of Neurology, the First People's Hospital of Huzhou, First affiliated Hospital of Huzhou University) ;
  • Xufeng Zhang (Department of Neurology, the First People's Hospital of Huzhou, First affiliated Hospital of Huzhou University) ;
  • Ruiqi Zeng (Department of Neurology, the First People's Hospital of Huzhou, First affiliated Hospital of Huzhou University) ;
  • Dan Chen (Department of Neurology, the First People's Hospital of Huzhou, First affiliated Hospital of Huzhou University) ;
  • Jingjing Yao (Department of Neurology, the First People's Hospital of Huzhou, First affiliated Hospital of Huzhou University) ;
  • Jingjing Min (Department of Neurology, the First People's Hospital of Huzhou, First affiliated Hospital of Huzhou University)
  • Received : 2023.03.10
  • Accepted : 2023.11.05
  • Published : 2024.04.15
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Abstract

Chronic renal failure (CRF) resulting in vascular calcification, which does damage to blood vessels and endothelium, is an independent risk factor for stroke. It has been reported that cilostazol has a protective effect on the focal cerebral ischemic infarct. However, its impact on vascular injury in CRF combined stroke and its molecular protection mechanism have not been investigated. In this study, we carried out the effect of cilostazol on CRF combined stroke rats, and the results confirmed that it improved the neurobehavior, renal function as well as pathologic changes in both the kidney and brain. In addition, the inflammation and oxidative stress factors in the kidney and brain were suppressed. Moreover, the rates of brain edema and infarction were decreased. The injured brain-blood barrier (BBB) was recovered with less Evans blue extravasation and more expressions of zonula occludens-1(ZO-1) and occludin. More cerebral blood flow (CBF) in the ipsilateral hemisphere and more expression of CD31 and vascular endothelial growth factor (VEGF) in brain and kidney were found in the cilostazol group. Furthermore, cell apoptosis and cell autophagy became less, on the contrary, proteins of vascular endothelial growth factor receptor 2 (VEGFR2) after the cilostazol treatment were increased. More importantly, this protective effect is related to the pathway of Janus Kinase (JAK)/signal transducer and activator of transcription 3 (STAT3), mammalian target of rapamycin (mTOR), and the hypoxia inducible factor-1α (HIF-1α). In conclusion, our results confirmed that cilostazol exerted a protective effect on the brain and kidney function, specifically in vascular injury, oxidative stress, cell apoptosis, cell autophagy, and inflammation response in CRF combined with stroke rats which were related to the upregulation of JAK/STAT3/mTOR signal pathway.

Keywords

Acknowledgement

This study was supported by Huzhou Municipal Science and Technology Bureau Public Welfare Application Research Project under Grant Numbers (2021GZB12, 2021GYB54, 2019GZ40), Zhejiang Medicine and Health Science and Technology Project under Grant Numbers (2020RC118, 2021KY1097).

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