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Mechanism of Emulsified Isoflurane Postconditioning–Induced Activation of the Nrf2–Antioxidant Response Element Signaling Pathway During Myocardial Ischemia-Reperfusion

The Relationship With Reactive Oxygen Species

Chen, Wei, MA*; Chen, Xi-Yuan, MA*; Wang, Ying, MA*; Wang, Hai-Ying, MD*; Zhou, Wen-Jing, MA*; Yu, Tian, PhD

Journal of Cardiovascular Pharmacology: May 2019 - Volume 73 - Issue 5 - p 265–271
doi: 10.1097/FJC.0000000000000668
Original Article
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Abstract: Emulsified isoflurane (EI) has been shown to alleviate myocardial ischemia-reperfusion (IR) injury. However, previous reports have not been focused on the underlying mechanism. We used models of IR injury in Langendorff-isolated rat hearts to determine the relationship between the mechanism underlying EI postconditioning (EIP)-induced activation of the nuclear factor-E2–related factor 2 (Nrf2)-antioxidant response element signaling pathway during myocardial IR, and its relationship with reactive oxygen species. In comparison with the IR group, the EIP group showed a significant reduction in myocardial ultrastructural damage, significant increase in function [heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure, and maximal rate of the increase in left ventricular pressure (+dp/dtmax)], and upregulated expression of Nrf2, HO-I, NQO1, and SOD1 mRNA and proteins at the end of reperfusion. After treatment with N-(2-mercaptopropionyl)-glycine (MPG), the significant reduction in myocardial ultrastructural damage and significant increases in function, and mRNA and protein expression were no longer evident in the M + EIP group. These results show that EIP can regulate reactive oxygen species levels and activate the Nrf2–antioxidant response element signaling pathway, thereby attenuating myocardial IR injury in rats.

*Department of Anesthesiology, the Affiliated Hospital of Zunyi Medical College, Guizhou, China; and

Key laboratory of anesthesia and organ protection, Zunyi Medical College, Guizhou, China.

Reprints: Hai-Ying Wang, MD, Department of Anesthesiology, the Affiliated Hospital of Zunyi Medical College, Dalian Rd, Huichuan District, Zunyi 563000, Guizhou Province, China (e-mail: wanghaiting-8901@163.com).

The National Natural Sciences Foundation of China (reference: 30960366).

The authors report no conflicts of interest.

W. Chen and X.-Y. Chen contributed equally to this article.

Received December 06, 2018

Accepted February 04, 2019

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