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Dingxin Recipe (定心方) prevents ischemia/reperfusion-induced arrhythmias via up-regulating prohibitin and suppressing inflammatory responses

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Abstract

Objective

To identify the underlying mechanisms of the protective effects of Dingxin Recipe (定: 心方, DXR), a Chinese compound prescription that has been used clinically in China for more than 20 years, on ischemia/reperfusion (I/R)-induced arrhythmias in rat model.

Methods

A total of 30 rats were randomly divided into three groups: sham group, I/R group, and DXR-pretreated I/R (DXR-I/R) group. Rats in the DXR-DXRI/R group were intragastrically administrated with DXR (12.5 g/kg per day) for consecutive 7 days, while rats I/in the sham and I/R groups were administrated with normal saline. Arrhythmias were introduced by I/R and electrocardiograms (ECG) were recorded. Two-dimensional (2-D) polyacrylamide gel electrophoresis and matrix-matrixassisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify assisted differentially expressed proteins. Immunohistochemistry, real-time quantitative polymerase chain reaction (RQ-RQPCR), Western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to analyze proteins PCR), obtained in the above experiments.

Results

DXR significantly reduced the incidence and mean duration of ventricular tachycardia and ventricular fibrillation and dramatically decreased the mortality, as well as arrhythmia score, compared with those of the I/R group. Among successfully identified proteins, prohibitin (PHB) and heart fatty acid binding protein (hFABP) were up-regulated in DXR-pretreated I/R rats compared with those of the I/R rats. In addition, compared with the I/R group, the level of glutathione (GSH) was elevated accompanied by reduced expressions of interleukin-6 (IL-6) and neutrophil infiltration in I/R rats with DXR pretreatment.

Conclusions

DXR could alleviate I/R-induced arrhythmias, which might be related to increased expression of PHB. The enhanced expression of PHB prevented against the depletion of GSH and consequently inhibited apoptosis of cardiomyocytes. Furthermore, up-regulation of PHB might ameliorate I/R-induced cell death and leakage of hFABP by suppressing neutrophil infiltration and IL-6 expressions.

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Authors and Affiliations

  1. The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China

    Yu-hua Jia  (贾钰华), Li-jun Li  (李丽君), Ya-wei Liu  (刘亚伟), Chun-hua Li  (黎春华), Xiu-qiong Fu  (符秀琼) & Xue-gang Sun  (孙学刚)

  2. Fuda Cancer Hospital, Guangzhou, 510300, China

    Yun-xian Zhang  (张云仙)

  3. Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510120, China

    Ping Zeng  (曾 平)

  4. The Institute of Integrated Traditional Chinese and Western Medicine, Sun Yatsen University, Guangzhou, 510120, China

    Wei-kang Wu  (吴伟康)

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  1. Yu-hua Jia  (贾钰华)
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  6. Xiu-qiong Fu  (符秀琼)
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  7. Ping Zeng  (曾 平)
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  8. Wei-kang Wu  (吴伟康)
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  9. Xue-gang Sun  (孙学刚)
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Correspondence to Xue-gang Sun  (孙学刚).

Additional information

Supported by the National Natural Science Foundation of China (No. 30572435 and No. 81072776) and Baiyun District Science and Technology Program (No. 2010-KZ-39)

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Jia, Yh., Zhang, Yx., Li, Lj. et al. Dingxin Recipe (定心方) prevents ischemia/reperfusion-induced arrhythmias via up-regulating prohibitin and suppressing inflammatory responses. Chin. J. Integr. Med. 18, 120–129 (2012). https://doi.org/10.1007/s11655-012-0998-x

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  • DOI: https://doi.org/10.1007/s11655-012-0998-x

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