Neuroprotection of rhGLP-1 in diabetic rats with cerebral ischemia/reperfusion injury via regulation of oxidative stress, EAAT2, and apoptosis

被引：29

作者：

Fang, Yi ^{[1
]}

Jiang, Daoli ^{[2
]}

Wang, Yitong ^{[1
,3
]}

Wang, Qian ^{[1
]}

Lv, Dongmei ^{[2
]}

Liu, Jichao ^{[4
]}

Liu, Chang ^{[5
]}

机构：

[1] Peking Univ, Peoples Hosp, Dept Pharm, Beijing, Peoples R China

[2] Xuzhou Med Univ, Affiliated Hosp, Dept Pharm, 99 Huaihai West Rd, Xuzhou 221006, Jiangsu, Peoples R China

[3] Peking Univ, Dept Pharm Adm & Clin Pharm, Hlth Sci Ctr, Beijing, Peoples R China

[4] Peking Univ, Anim Expt Ctr, Peoples Hosp, Beijing, Peoples R China

[5] Xuzhou Med Univ, Jiangsu Key Lab New Drug Res & Clin Pharm, Xuzhou, Jiangsu, Peoples R China

来源：

DRUG DEVELOPMENT RESEARCH | 2018年 / 79卷 / 06期

关键词：

cerebral ischemia; reperfusion injury; diabetes; rhGLP-1; GLUCAGON-LIKE PEPTIDE-1; ACUTE ISCHEMIC-STROKE; GLIAL GLUTAMATE TRANSPORTER; PROTECTS HIPPOCAMPAL-NEURONS; RECEPTOR STIMULATION; ALZHEIMERS-DISEASE; SIGNAL-TRANSDUCTION; HYPOXIA-ISCHEMIA; BRAIN ISCHEMIA; GLP-1;

D O I：

10.1002/ddr.21439

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

The purpose of the present study is to evaluate the neuroprotective effect of recombinant human glucagon-like peptide-1 (rhGLP-1) as well as to explore corresponding mechanisms in diabetic rats with cerebral ischemia/reperfusion injury induced by middle cerebral artery occlusion (MCAO). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. The rats were pretreated with rhGLP-1 (20g/kg intraperitoneally, thrice a day) for 14days. Thereafter, the rats were subjected to MCAO 90min/reperfusion 24hr. At 2 and 24hr of reperfusion, the rats were assessed for neurological deficits and subsequently executed for the evaluation of cerebral infarct volume, oxidative stress parameters, and the expression of excitatory amino acid transporter 2 (EAAT2) and apoptotic markers. Results indicate that rhGLP-1 significantly ameliorated neurological deficits and reduced cerebral infarct volume in diabetic MCAO rats. In addition, oxidative stress parameters in ischemic penumbra were significantly alleviated in rhGLP-1-pretreated diabetic MCAO rats. rhGLP-1 significantly upregulated the ratio of Bcl-2/Bax and EAAT2 expression and downregulated cleaved caspase-3 expression in ischemic penumbra of diabetic MCAO rats. Our results suggest that rhGLP-1 could significantly ameliorate neurological deficits and reduce cerebral infarct volume in diabetic MCAO rats, which may be due to the inhibition of oxidative stress and apoptosis and the promotion of EAAT2 expression.

引用

页码：249 / 259

页数：11

共 72 条

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