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Korean J Physiol Pharmacol 2017 Sep; 21(5): 475-485
Yi Fang1,#, Xiaofang Liu2,#, Libo Zhao1, Zhongna Wei3, Daoli Jiang4, Hua Shao2, Yannan Zang1, Jia Xu5, Qian Wang1, Yang Liu1, Ye Peng6, and Xiaoxing Yin4,*
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
1Department of Pharmacy, Peking University People’s Hospital, Beijing 100044, 2Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, 3Department of Pharmacy, Guizhou Orthopedics Hospital, Guizhou 550002, 4Department of Pharmacy, Xuzhou Medical University, Xuzhou 221004, 5Department of Pharmacy, Mawangdui Hospital, Changsha 410016, 6Department of oncology, Harrison International Peace Hospital, Hengshui 053000, China
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 μg/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.
Keyword : Brain ischemia/reperfusion, Diabetic rats, Nrf2/HO-1, rhGLP-1 (7-36)