Pharmaceutical Biology (Jan 2018)

Effect of simvastatin on the SIRT2/NF-κB pathway in rats with acute pulmonary embolism

  • Zhi-Yao Wu,
  • Hui Li,
  • Yong-Jun Tang

DOI
https://doi.org/10.1080/13880209.2018.1508239
Journal volume & issue
Vol. 56, no. 1
pp. 511 – 518

Abstract

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Context: Statins have been widely used in acute pulmonary embolism (APE), while simvastatin has been well-established for the prevention of pulmonary hypertension, which was supposed to be an attractive recommendation for APE treatment. Objective: The current article studies the effect of simvastatin on the SIRT2/NF-κB pathway in rats with APE. Materials and methods: Sprague-Dawley rats were divided into four groups (n = 24 per group): control group, rats were treated with saline once daily for 14 days before administration of saline (sham group) or a suspension of autologous emboli (APE group), or rats were treated with simvastatin (10 mg/kg) for 14 days before administration of autologous emboli (APE + simvastatin) group. The RVSP, mPAP and the arterial blood gas was analyzed. Besides, plasma inflammatory cytokines and MMPs levels, as well as the expression of SIRT2/NF-κB pathway were determined. Results: Compared with the control and sham groups, the levels of mPAP (31.06 ± 3.47 mmHg), RVSP (35.12 ± 6.02 mmHg), A-aDO2 (33.14 ± 6.16 mmHg) and MMP-9 (6.89 ± 0.84 ng/mL) activity were significantly elevated, but PaO2 (66.87 ± 7.85 mmHg) was highly decreased in rats from APE group at 24 h after APE. Meanwhile, the inflammatory changes were aggravated by the enhanced levels of TNF-α (138.85 ± 22.69 pg/mL), IL-1β (128.47 ± 22.14 pg/mL), IL-6 (103.16 ± 13.58 pg/mL) and IL-8 (179.28 ± 25.79 pg/mL), as well as increased NF-κB (5.29 ± 0.47 fold), but reduced SIRT2 (59 ± 6% reduction), and eNOS (61 ± 5% reduction) mRNA in APE rats. APE rats treated with simvastatin led to a significant opposite trend of the above indexes. Conclusions: Simvastatin protects against APE-induced pulmonary artery pressure, hypoxemia and inflammatory changes probably due to the regulation of SIRT2/NF-κB signalling pathway, which suggest that simvastatin may have promising protective effects in patients with APE.

Keywords