Protective Mechanism of Tempol on Hypobaric Hypoxia-Induced Heart Damage in Mice
MA Hui-ping, JING Lin-lin*, HE Lei, FAN Peng-cheng, JIA Zheng-ping
Department of Pharmacy, Lanzhou General Hospital, Lanzhou Command of PLA; Key Lab of PLA for Prevention and Treatment of Injuries Induced by High Altitude, Lanzhou 730050, China
Abstract��OBJECTIVE To study the effect mechanism of tempol against hypobaric hypoxia-induced heart damage in mice. METHODS One hundred and ten BALB/c mice were randomly divided into normal control group, hypoxia model group, acetazolamide group and tempol group. After single intraperitoneal injection for 30 min, the mice were exposed to a simulated high altitude of 8 000 m for 12 h. After hypoxic exposure, blood was collected from the eye sockets and separated into serum to measure the activities of lactic dehydrogenase (LDH)and creatine kinase (CK). Then the mice were sacrificed and the content of H2O2 and malondialdehyde (MDA) as well as ATPase and antioxidant enzyme activity in heart were determined. HIF-1, VEGF, Nrf2, and HO-1 were detected by immunohistochemistry. RESULTS Compared with normal control group, the activities of plasma CK and LDH in hypoxia model group significantly increased. In addition, the content of H2O2 and MDA in hypoxia model group significantly increased while ATPase and antioxidant enzymes activity markedly decreased compared with the normal control group. Moreover, the expression of HIF-1��, VEGF, Nrf2 and HO-1 increased. Prior administration of tempol effectively decreased the activities of plasma CK and LDH as well as the content of H2O2 and MDA in heart tissue. Tempol could increase ATPase and antioxidant enzyme activities and decreased the expression of HIF-1�� and VEGF compared with hypoxia model, while it could further increase the expression of Nrf2 and HO-1. CONCLUSION Tempol has protective effect on heart injury induced by hypobaric hypoxia in mice. Its mechanism may be attributed to the amelioration of energy metabolism, scavenging free radical, improvement of antioxidant enzyme activity the activation of the Nrf2/HO-1 pathway as well as alleviation of oxidative stress.
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MA Hui-ping, JING Lin-lin, HE Lei, FAN Peng-cheng, JIA Zheng-ping. Protective Mechanism of Tempol on Hypobaric Hypoxia-Induced Heart Damage in Mice. Chinese Pharmaceutical Journal, 2017, 52(18): 1597-1603.
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2017, Vol. 52 
