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http://dx.doi.org/10.4196/kjpp.2021.25.4.281

Whole body hypoxic preconditioning-mediated multiorgan protection in db/db mice via nitric oxide-BDNF-GSK-3β-Nrf2 signaling pathway  

Li, Yuefang (Cadre Ward the No.901 Hospital of the Joint Logistics Support Unit of the Chinese People's Liberation Army)
Huang, Yan (Cadre Ward the No.901 Hospital of the Joint Logistics Support Unit of the Chinese People's Liberation Army)
Cheng, Xi (Cadre Ward the No.901 Hospital of the Joint Logistics Support Unit of the Chinese People's Liberation Army)
He, Youjun (Cadre Ward the No.901 Hospital of the Joint Logistics Support Unit of the Chinese People's Liberation Army)
Hu, Xin (Cadre Ward the No.901 Hospital of the Joint Logistics Support Unit of the Chinese People's Liberation Army)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.25, no.4, 2021 , pp. 281-296 More about this Journal
Abstract
The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetes-induced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholine-induced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O2 for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (L-NAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IR-induced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.
Keywords
Brain-derived neurotrophic factor; Dementia; Heart; Ischemia; Myocardial infarction; Nitric oxide;
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