Diabetes mellitus aggravates cerebral ischemia injury in rats by downregulating VEGF/VEGFR2 pathway

Junjiang Lu ,Joungho Han ,Jing He ,Yadan Fan ,Caihong Deng ,Ling Chen

doi:10.3760/cma.j.issn.1673-4165.2016.07.006

Junjiang Lu , Joungho Han + Show 4 more

https://doi.org/10.3760/cma.j.issn.1673-4165.2016.07.006

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Objective To 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. Methods A 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. Results In 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. Conclusions VEGF/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

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