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Article

Tissue kallikrein protects against ischemic stroke by suppressing TLR4/NF-κB and activating Nrf2 signaling pathway in rats

  • Authors:
    • Jiawei Yang
    • Jianhua Su
    • Fen Wan
    • Nan Yang
    • Haibo Jiang
    • Mingming Fang
    • Hang Xiao
    • Jun Wang
    • Jinrong Tang
  • View Affiliations / Copyright

    Affiliations: Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Neurology, The Affiliated Jintan Hospital of Medical College of Jiangsu University, Jintan, Jiangsu 213200, P.R. China, Department of Neurology, Jiangsu Hospital of Chinese Traditional and Western Medicine, Nanjing, Jiangsu 210028, P.R. China, Department of Neurotoxicology, Nanjing Medical University, Nanjing, Jiangsu 211199, P.R. China
  • Pages: 1163-1170
    |
    Published online on: June 15, 2017
       https://doi.org/10.3892/etm.2017.4614
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Abstract

Brain damage following cerebral ischemia-reperfusion (I/R) is a complicated pathophysiological course, in which inflammation and oxidative stress have been suggested to serve an important role. Toll‑like receptor 4 (TLR4) has been suggested to be involved in secondary inflammatory process in cerebral ischemia. Nuclear factor erythroid 2-related factor 2 (Nrf2), an important regulator of the antioxidant host defense, maintains the cellular redox homeostasis. Tissue kallikrein (TK) has been proven to elicit a variety of biological effects in ischemic stroke through its anti‑inflammatory and anti‑oxidant properties. However, the mechanisms underlying its beneficial effects remain poorly defined. The present study examined the hypothesis that TK attenuates ischemic cerebral injury via the TLR4/nuclear factor‑κB (NF‑κB) and Nrf2 signaling pathways. Using a transient rat middle cerebral artery occlusion (MCAO) model, the effects of immediate and delayed TK treatment subsequent to reperfusion were investigated. The neurological deficits, infarct size, and the expression of TLR4/NF‑κB and Nrf2 pathway in ischemic brain tissues were measured at 24 following MCAO. The results indicated that TK immediate treatment significantly improved neurological deficits and reduced the infarct size, accompanied by the inhibition of TLR4 and NF‑κB levels, and the activation of Nrf2 pathway. Furthermore, TK delayed treatment also exerted neuroprotection against I/R injury. However, the neuroprotective effect of TK immediate treatment was better compared with that of TK delayed treatment. In conclusion, the results indicated that TK protected the brain against ischemic injury in rats after MCAO through its anti‑oxidative and anti‑inflammatory effects. Suppression of TLR4/NF‑κB and activation of the Nrf2 pathway contributed to the neuroprotective effects induced by TK in cerebral ischemia. Therefore, TK may provide an effective intervention with a wider therapeutic window for ischemic stroke.
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Copy and paste a formatted citation
Spandidos Publications style
Yang J, Su J, Wan F, Yang N, Jiang H, Fang M, Xiao H, Wang J and Tang J: Tissue kallikrein protects against ischemic stroke by suppressing TLR4/NF-κB and activating Nrf2 signaling pathway in rats. Exp Ther Med 14: 1163-1170, 2017.
APA
Yang, J., Su, J., Wan, F., Yang, N., Jiang, H., Fang, M. ... Tang, J. (2017). Tissue kallikrein protects against ischemic stroke by suppressing TLR4/NF-κB and activating Nrf2 signaling pathway in rats. Experimental and Therapeutic Medicine, 14, 1163-1170. https://doi.org/10.3892/etm.2017.4614
MLA
Yang, J., Su, J., Wan, F., Yang, N., Jiang, H., Fang, M., Xiao, H., Wang, J., Tang, J."Tissue kallikrein protects against ischemic stroke by suppressing TLR4/NF-κB and activating Nrf2 signaling pathway in rats". Experimental and Therapeutic Medicine 14.2 (2017): 1163-1170.
Chicago
Yang, J., Su, J., Wan, F., Yang, N., Jiang, H., Fang, M., Xiao, H., Wang, J., Tang, J."Tissue kallikrein protects against ischemic stroke by suppressing TLR4/NF-κB and activating Nrf2 signaling pathway in rats". Experimental and Therapeutic Medicine 14, no. 2 (2017): 1163-1170. https://doi.org/10.3892/etm.2017.4614
Copy and paste a formatted citation
x
Spandidos Publications style
Yang J, Su J, Wan F, Yang N, Jiang H, Fang M, Xiao H, Wang J and Tang J: Tissue kallikrein protects against ischemic stroke by suppressing TLR4/NF-κB and activating Nrf2 signaling pathway in rats. Exp Ther Med 14: 1163-1170, 2017.
APA
Yang, J., Su, J., Wan, F., Yang, N., Jiang, H., Fang, M. ... Tang, J. (2017). Tissue kallikrein protects against ischemic stroke by suppressing TLR4/NF-κB and activating Nrf2 signaling pathway in rats. Experimental and Therapeutic Medicine, 14, 1163-1170. https://doi.org/10.3892/etm.2017.4614
MLA
Yang, J., Su, J., Wan, F., Yang, N., Jiang, H., Fang, M., Xiao, H., Wang, J., Tang, J."Tissue kallikrein protects against ischemic stroke by suppressing TLR4/NF-κB and activating Nrf2 signaling pathway in rats". Experimental and Therapeutic Medicine 14.2 (2017): 1163-1170.
Chicago
Yang, J., Su, J., Wan, F., Yang, N., Jiang, H., Fang, M., Xiao, H., Wang, J., Tang, J."Tissue kallikrein protects against ischemic stroke by suppressing TLR4/NF-κB and activating Nrf2 signaling pathway in rats". Experimental and Therapeutic Medicine 14, no. 2 (2017): 1163-1170. https://doi.org/10.3892/etm.2017.4614
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