Ulinastatin protects cardiomyocytes against ischemia‑reperfusion injury by regulating autophagy through mTOR activation

Xiao,Jian; Zhu,Xiaoyan; Ji,Guangyu; Yang,Qian; Kang,Bo; Zhao,Jianquan; Yao,Feng; Wu,Lihui; Ni,Xin; Wang,Zhinong

doi:10.3892/mmr.2014.2450

October 2014 Volume 10 Issue 4

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October 2014 Volume 10 Issue 4

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Article

Ulinastatin protects cardiomyocytes against ischemia‑reperfusion injury by regulating autophagy through mTOR activation

Authors:
- Jian Xiao
- Xiaoyan Zhu
- Guangyu Ji
- Qian Yang
- Bo Kang
- Jianquan Zhao
- Feng Yao
- Lihui Wu
- Xin Ni
- Zhinong Wang
View Affiliations / Copyright

Affiliations: Department of Cardiothoracic Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, P.R. China, Department of Physiology, The Second Military Medical University, Shanghai 200433, P.R. China, Department of Anesthesiology, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200030, P.R. China
Pages: 1949-1953
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Published online on: August 5, 2014

https://doi.org/10.3892/mmr.2014.2450
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Abstract

Autophagy is significant in myocardial ischemia‑reperfusion (IR) injury. Ulinastatin has been demonstrated to protect cardiomyocytes against IR through inducing anti‑inflammatory effects. However, whether ulinastatin has an anti‑autophagic effect is yet to be elucidated. The present study aimed to investigate the effect of ulinastatin on the regulation of autophagy during IR injury. Cardiomyocytes of neonatal rats were randomly divided into control, hypoxia‑reoxygenation (HR) and ulinastatin groups. In order to investigate whether mammalian target of rapamycin (mTOR) is involved in mediating the protective effect of ulinastatin, cells were treated with the mTOR inhibitor, rapamycin 30 min prior to ulinastatin treatment. To demonstrate the anti‑autophagic effect of ulinastatin in vivo, a rat IR model was established. Ulinastatin (1x104 U/kg body weight) was administered 30 min prior to the induction of IR via peritoneal injection. Light chain 3 (LC3), phosphorylated (p)‑mTOR, p‑protein kinase B (Akt) and p‑P70S6 kinase (p‑P70S6K) protein expression were assessed using western blot analysis. In addition, cell vitality, myocardial infarct size and lactate dehydrogenase (LDH) levels were measured. LC3‑Ⅱ protein expression was found to be downregulated, while p‑Akt, p‑mTOR and p‑P70S6K protein expression were observed to be upregulated by ulinastatin. In addition, cell vitality was found to increase and LDH was observed to decrease in the ulinastatin group compared with the HR group in vitro. Furthermore, rapamycin was found to attenuate the myocardial protective effect that is induced by ulinastatin. In vivo, ulinastatin was found to downregulate LC3‑Ⅱ protein expression, and reduce myocardium infarct size and LDH serum levels. These findings indicate that ulinastatin exhibits a myocardial protective effect against IR injury by regulating autophagy through mTOR activation.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Ulinastatin protects cardiomyocytes against ischemia‑reperfusion injury by regulating autophagy through mTOR activation

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