Cardiovascular Journal of Africa: Vol 31 No 1 (January/February 2020)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 31, No 1, January/February 2020 AFRICA 25
Salidroside protects the cardiac function of exhausted
rats by inducing Nrf2 expression
Peng Xu, Yang Wang, Weiwei Sun, Yawei Sun, Wei Lu, Yumei Chang, Zheng Ping, Yang Li, Xuebin Cao
Abstract
Objective: To investigate whether salidroside (Sal) protected the
rat heart from exhaustive exercise-induced injury by inducing
nuclear factor erythroid 2-related factor 2 (Nrf2) expression.
Methods: Forty-eight male Sprague-Dawley rats were divided
into four groups (n = 12 rats per group): the control, the
exhaustive swimming (ES) group, the low-dose Sal plus acute
exhaustive swimming (SLE) group, and the high-dose Sal plus
acute exhaustive swimming (SHE) group. In the SLE and
SHE groups, 15and 30mg/kg Sal were administered, respec-
tively, once a day. The rats in the control and ES groups were
administered the same amount of physiological saline, respec-
tively, once a day. On the 14th day, the rats in the ES, SLE and
SHE groups underwent exhaustive swimming training once.
Then cardiac function parameters and electrocardiograms
were recorded. Biomarkers of myocardial injury in the serum
and oxidative stress factors in the myocardial tissue were
evaluated using ELISA tests. The levels of Nrf2, nuclear Nrf2
and Kelch-like ECH-associated protein 1 (Keap1) messenger
RNA and proteins were assessed in the myocardium using
q-PCR and Western blotting, respectively.
Results: Compared to the control group, the ES group showed
remarkable increases in serum brain natriuretic peptide
(BNP), cardiac troponin I (cTnI) and reactive oxygen species
levels, but significant decreases in catalase and glutathione
levels (p < 0.05). Compared to the ES group, the Sal treat-
ment decreased serum BNP and cTnI levels and allevi-
ated the changes in levels of oxidative stress-related factors.
After treatment with Sal, nuclear and intracellular levels
of Nrf2 protein were increased in the myocardial cells,
while the level of Keap1 protein was decreased (p < 0.05).
Conclusion: Sal protected the heart from exhaustive exercise-
induced injury, and it may improve cardiac function and
cardiac bioelectricity in exhausted rats by inducing Nrf2
expression.
Keywords: exhaustive exercise, heart function, nuclear factor
erythroid 2-related factor 2, oxidative stress, rats
Submitted 10/4/19, accepted 14/7/19
Published online 2/10/19
Cardiovasc J Afr 2020; 31: 25–32
DOI: 10.5830/CVJA-2019-043
High-intensity exercise, such as exhaustive exercise (exercise
intensity or duration exceeding the body’s limit), not only
influences performance in competition but also impairs the
physical and mental health of athletes and military personnel.1
Therefore it is important to explore performance and the
pathogenesis of exercise-induced heart injury to improve its
treatment.
Exhaustive exercise can cause destruction of the myocardial
ultrastructure, abnormal energy metabolism and a reduction in
cardiac function and electrocardio-electric changes.2,3 Exhaustive
exercise also increases oxidative stress levels, potentially causing
heart damage. 4
Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a
leading role in activating or encoding anti-oxidant enzymes and
an important role in regulating the oxidation–anti-oxidation
states of cardiac and vascular endothelial cells.5,6 High-intensity
exercise affects Nrf2 levels, but the effect remains controversial.
Acute intense exercise increased the messenger RNA (mRNA)
transcription of Nrf2 target genes in skeletal muscle and most
antioxidant enzyme genes in cardiac myocytes in mice.7,8 Levels
of Nrf2 protein exhibited little change in the skeletal muscle of
rats exposed to exhaustive treadmill exercise, and the expression
and enzyme activity of its target proteins also exhibited little or
decreased change. 9
Kelch-like ECH-associated protein 1 (Keap1) is a negative
regulator of Nrf2. In response tooxidative stress, a conformational
change in Keap1 causes Nrf2 to dissociate from Keap1, which
is the most common method for activating Nrf2. 10 Upon
activation, Nrf2 is transported to the nucleus, then antioxidant
enzyme-encoding genes are expressed.11 The expression of the
antioxidant enzymes superoxide dismutase (SOD), glutathione
(GSH) and catalase (CAT) is mainly induced by activated Nrf2.
Exhaustive exercise also increases oxidative stress levels.
Reactive oxygen species (ROS) activate the stress-response
kinases in the MAPK family;12 many protein kinases, such as the
extracellular signal-regulating kinase (ERK) and p38MAPK are
located upstream of Nrf2.13,14 These kinases phosphorylate Nrf2
Department of Cardiology, No. 252 Hospital of the Chinese
People’s Liberation Army, Baoding, Hebei, China
Peng Xu,
Weiwei Sun, MD
Zheng Ping, MD
Xuebin Cao, MD,
Department of Clinical Pharmacy, No. 252 Hospital of the
Chinese People’s Liberation Army, Baoding, Hebei, China
Yang Wang, MD
Department of Central Laboratory, No. 252 Hospital of the
Chinese People’s Liberation Army, Baoding, Hebei, China
Yawei Sun, MD
Yumei Chang, MD
Department of Emergency, Baoding First Hospital,
Baoding, Hebei, China
Wei Lu, MD
Department of Cardiology, Chinese People’s Liberation
Army General Hospital, Beijing, China
Yang Li, MD,