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http://dx.doi.org/10.4196/kjpp.2017.21.5.475

RhGLP-1 (7-36) protects diabetic rats against cerebral ischemia-reperfusion injury via up-regulating expression of Nrf2/HO-1 and increasing the activities of SOD  

Fang, Yi (Department of Pharmacy, Peking University People's Hospital)
Liu, Xiaofang (Zhongda Hospital, School of Medicine, Southeast University)
Zhao, Libo (Department of Pharmacy, Peking University People's Hospital)
Wei, Zhongna (Department of Pharmacy, Guizhou Orthopedics Hospital)
Jiang, Daoli (Department of Pharmacy, Xuzhou Medical University)
Shao, Hua (Zhongda Hospital, School of Medicine, Southeast University)
Zang, Yannan (Department of Pharmacy, Peking University People's Hospital)
Xu, Jia (Department of Pharmacy, Mawangdui Hospital)
Wang, Qian (Department of Pharmacy, Peking University People's Hospital)
Liu, Yang (Department of Pharmacy, Peking University People's Hospital)
Peng, Ye (Department of oncology, Harrison International Peace Hospital)
Yin, Xiaoxing (Department of Pharmacy, Xuzhou Medical University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.21, no.5, 2017 , pp. 475-485 More about this Journal
Abstract
The present study aimed to explore the neuroprotective effect and possible mechanisms of rhGLP-1 (7-36) against transient ischemia/reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in type 2 diabetic rats. First, diabetic rats were established by a combination of a high-fat diet and low-dose streptozotocin (STZ) (30 mg/kg, intraperitoneally). Second, they were subjected to MCAO for 2 h, then treated with rhGLP-1 (7-36) (10, 20, $40{\mu}g/kg$ i.p.) at the same time of reperfusion. In the following 3 days, they were injected with rhGLP-1 (7-36) at the same dose and route for three times each day. After 72 h, hypoglycemic effects were assessed by blood glucose changes, and neuroprotective effects were evaluated by neurological deficits, infarct volume and histomorphology. Mechanisms were investigated by detecting the distribution and expression of the nuclear factor erythroid-derived factor 2 related factor 2 (Nrf2) in ischemic brain tissue, the levels of phospho-PI3 kinase (PI3K)/PI3K ratio and heme-oxygenase-1 (HO-l), as well as the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA). Our results showed that rhGLP-1 (7-36) significantly reduced blood glucose and infarction volume, alleviated neurological deficits, enhanced the density of surviving neurons and vascular proliferation. The nuclear positive cells ratio and expression of Nrf2, the levels of P-PI3K/PI3K ratio and HO-l increased, the activities of SOD increased and the contents of MDA decreased. The current results indicated the protective effect of rhGLP-1 (7-36) in diabetic rats following MCAO/R that may be concerned with reducing blood glucose, up-regulating expression of Nrf2/HO-1 and increasing the activities of SOD.
Keywords
Brain ischemia/reperfusion; Diabetic rats; Nrf2/HO-1; rhGLP-1 (7-36);
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