title: Protective effect of rhGLP-1 (7-36) on brain ischemia/reperfusion damage in diabetic rats.
abstract: In recent years, GLP-1 and its analogs have been developed for the treatment of type 2 diabetes. It has been reported that stimulating the GLP-1 receptor can protect neurons against metabolic and oxidative insults, and therefore can be used in the treatment of stroke and Parkinson׳s disease. The present study aimed to examine the neuroprotective effects of rhGLP-1 (7-36) and its possible mechanisms against acute ischemia/reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in diabetic rats. The type 2 diabetic rat model was established by a combination of a high-fat diet and low-dose streptozotocin (STZ). RhGLP-1 (7-36) (20, 40, 80μg/kg) was given intraperitoneally before reperfusion. The neuroprotective effects of rhGLP-1 (7-36) were evaluated by changes in neurological deficit scores and 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Changes in blood glucose were used to assess hypoglycemic effects. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), inducible nitric oxide syntheses (iNOS) and endothelial nitric oxide syntheses (eNOS) after MCAO/R administration (2h and 46h) were examined to investigate the possible mechanisms of RhGLP-1 (7-36). Haematoxylin and eosin (H&E) staining was used for histopathological observation. Compared with the control group, rhGLP-1 (7-36)-treated groups decreased nerve function deficiency scores; significantly reduced infarction volume percentage, MDA, iNOS and blood glucose; and significantly increased SOD, GSH-PX and eNOS. In addition, rhGLP-1 (7-36) groups enhanced the density of surviving neurons and increased vascular proliferation. The current study suggests a neuroprotective effect of rhGLP-1 (7-36) in diabetic MCAO/R rats since anti-oxidative and anti-nitrosative stress effects can contribute to beneficial effects against ischemia/reperfusion injury.
authors.affiliation: Department of Pharmacy, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Mawangdui Hospital, Changsha, 410016, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The First Hospital, Huhhot, 010010, China.
authors.forename: Zhonglian
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Department of Pharmacy, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Wanyu
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Pharmacy, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Pharmacy, Peking University People's Hospital, Beijing 100044, China. Electronic address: phaseistudy@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D012720:Severity of Illness Index; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C061970:glucagon-like peptide 1 (7-36); D008315:Malondialdehyde; D052216:Glucagon-Like Peptide 1; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D013482:Superoxide Dismutase
keywords: Brain ischemia/reperfusion; Diabetic rats; GLP-1; Oxidative stress