Rosuvastatin reduces the pro-inflammatory effects of adriamycin on the expression of HMGB1 and RAGE in rats

Zhang,Haiyan; Lu,Xiang; Liu,Zhengxia; Du,Kang

doi:10.3892/ijmm.2018.3928

Rosuvastatin reduces the pro-inflammatory effects of adriamycin on the expression of HMGB1 and RAGE in rats

Authors:
- Haiyan Zhang
- Xiang Lu
- Zhengxia Liu
- Kang Du
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Affiliations: Department of Cardiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: October 11, 2018 https://doi.org/10.3892/ijmm.2018.3928
Pages: 3415-3423
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Rosuvastatin has cardiac protective effects through its anti‑inflammatory effects. The nuclear protein high‑mobility group box 1 (HMGB1) can activate inflammatory pathways when released from dying cells. The present study aimed to investigate the effects of rosuvastatin in adriamycin (ADR)‑treated rats. Adult male rats were randomized to three groups: i) Control group, ii) ADR group, and iii) ADR+rosuvastatin group. Serum biochemical indices were measured using an enzyme‑linked immunosorbent assay. Cardiac function was assessed by echocardiography. The expression of HMGB1 and receptors for advanced glycation end products (RAGE) were assessed by reverse transcription‑quantitative polymerase chain reaction analysis, western blot analysis, and immunohistochemistry. Cytokines were measured using flow cytometry. Rosuvastatin improved the biochemical indices and cardiac morphology and alleviated the pathological lesions. In the ADR+rosuvastatin group, the mRNA and protein levels of HMGB1 and RAGE in the myocardium were significantly lower compared with those in the ADR group (both P<0.05). The results showed that rosuvastatin significantly reduced the levels of HMGB1 and RAGE in the myocardium of the ADR‑treated rats. These results suggest that the protective effects of rosuvastatin may be associated with attenuation of the HMGB1/RAGE‑mediated inflammatory response in ADR‑treated rats. Despite this protective effect of rosuvastatin in the present study, it did not improve cardiac function in terms of the diastolic left ventricular internal dimension, systolic left ventricular internal dimension, left ventricular ejection fraction and left ventricular fractional shortening; this may be due the observation duration being insufficient.

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