Basic Researches
Diabetes mellitus aggravates cerebral ischemia injury in rats by downregulating VEGF/VEGFR2 pathway
Lu Junjiang, Han Jiangquan, Fan Yadan, Deng Caihong, He Jing, Chen Ling
Published 2016-07-28
Cite as Int J Cerebrovasc Dis, 2016,24(7): 611-616. DOI: 10.3760/cma.j.issn.1673-4165.2016.07.006
Abstract
ObjectiveTo investigate the effect of expressions of endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) in the ischemic cortex on ischemic cerebral injury in rats with diabetes mellitus.
MethodsA total of 36 healthy male Sprague-Dawley rats were divided into 3 groups: a sham-operation group, a cerebral ischemic group, and a diabetic cerebral ischemic group according to the random number table method. A diabetes model was induced by injection of streptozocin, and then, a permanent focal cerebral ischemic model was induced by the suture method. At 24 h after ischemia, the neurological deficit scores were conducted. The triphenyl tetrazolium chloride staining was used to measure the infarct volume. TUNEL was used to detect the apoptotic cells. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression levels of VEGF and VEGFR2 mRNAs. Western blot was used to detect the expression levels of VEGF and VEGFR2 proteins.
ResultsIn the sham operation group, there were no neurological deficit and infarcts, and there were only a few apoptotic cells and a few expressions of VEGF, VEGFR2 mRNAs and protein. The neurological function score (4.25±0.54 vs. 2.86±0.73) ; t=5.303, P<0.001), infarct volume (51.69±2.26 mm3vs. 30.15±2.08 mm3;t=23.166, P<0.001), and the number of apoptotic cells (24.22±1.34/HP vs. 13.28±0.37/HP; t=27.261, P<0.001) in the diabetic cerebral ischemia group were significantly increased than those in the cerebral ischemic group, while VEGF, VEGFR2 mRNA, and protein expression level were significantly decerased (VEGF mRNA: 4.74±0.54 vs. 6.71±0.91, P<0.001; VEGFR2 mRNA: 4.06±0.60 vs. 6.16±0.96, P<0.001, VEGF protein: 0.99±0.13 vs. 1.55±0.23, P<0.001; VEGFR2 protein: 4.12±0.74 vs. 6.23±0.76, P<0.001) compare with the cerebral ischemic group.
ConclusionsVEGF/VEGFR2 signal pathway participates in diabetes aggravating ischemic cerebral injury. The downregulating of VEGF/VEGFR2 may be one of the mechanisms of diabetes aggravating ischemic cerebral injury.
Key words:
Brain Ischemia; Diabetes Mellitus, Experimental; Vascular Endothelial Growth Factors; Vascular Endothelial Growth Factor Receptor-2; Apoptosis; Disease Models, Animal; Rats
Contributor Information
Lu Junjiang
Department of Neurology, the Fifth Affiliated Hospital of Zunyi Medical College, Zhuhai 519100, China
Han Jiangquan
Department of Neurology, the Fifth Affiliated Hospital of Zunyi Medical College, Zhuhai 519100, China
Fan Yadan
Department of Neurology, the Fifth Affiliated Hospital of Zunyi Medical College, Zhuhai 519100, China
Deng Caihong
Department of Neurology, the Fifth Affiliated Hospital of Zunyi Medical College, Zhuhai 519100, China
He Jing
Department of Neurology, the Fifth Affiliated Hospital of Zunyi Medical College, Zhuhai 519100, China
Chen Ling
Department of Neurology, the Fifth Affiliated Hospital of Zunyi Medical College, Zhuhai 519100, China; 3Kiang Wu Hospital, Macao, China
