高血糖和脑缺血对树鼩皮层不同区域VEGF表达的影响

目的：研究高血糖及局灶性脑缺血条件下，树鼩皮层不同区域VEGF表达的变化，探讨脑缺血、高血糖与VEGF之间的相互关系。方法：用链脲佐菌素复制树鼩高血糖模型，并建立光化学诱导皮层局灶性脑缺血，观察缺血4 h、24 h及72 h的病理形态学改变并计数海马神经元密度，用免疫组化法测定上述时间树鼩缺血中心区、半暗带、对侧皮层VEGF表达的动态变化。结果：形态学观察显示，光化学反应后4 h照射区皮层可见梗塞灶；24 h病损达高峰；72 h伴随胶质细胞增生等修复性反应。相应时点高血糖加缺血组的损伤大于缺血组，以缺血后24 h(P<0.01)和72 h(P<0.05)尤为显著。免疫组化染色表明，缺血后4 h皮层缺血半暗区可见VEGF表达增加， 24 h达高峰，72 h减弱；单纯高血糖也使VEGF表达上调；高血糖加缺血组VEGF表达强于单纯高血糖组(P<0.05)，但高血糖加缺血组与缺血组的同期值比较，无显著差异。结论：(1)在低等灵长类动物树鼩体内注射链脲佐菌素，并结合血栓性局部脑缺血方法学的应用能成功复制出实验性高血糖及脑缺血模型；(2)实验证明高血糖对局灶性脑缺血有恶化加重作用；(3)脑缺血及高血糖均可分别作为独立因素诱导VEGF的表达；但缺血与高血糖相加对VEGF表达未显示出叠加效应。

Effects of hyperglycemia and cerebral ischemia on VEGF expression in different subfield of cerebral cortex in tree shrews

AIM: To observe the changes of VEGF expression in different subfield of brain in tree shrews during hyperglycemia and focal cerebral ischemia, in order to explore the relationship between cerebral ischemia, hyperglycemia and VEGF. METHODS: High blood glucose in tree shrews was induced by intraperitoneal injection of streptozotoctin. Focal cortical thrombotic cerebral ischemia was induced by photochemical method in tree shrews. At 4 h, 24 h and 72 h after cerebral ischemia, the histopathological changes and hippocampal neuronal density were examined. VEGF expressions in the ischemic core, penumbra and contralateral cerebral cortex were detected by immunohistochemistry technique at different times after cerebral ischemia. RESULTS: The results of histopathological study showed that there was infarction zone in the exposured cerebral cortex at 4 h after photochemical reaction, and the damage was most severe at 24 h, subsequently accompanied with the glia multiplication and rehab reaction at 72 h. The animals in hyperglycemic ischemic group suffered from greater neurological lesion than the normoglycemic stroke animals, especially at 24 h (P<0.01) and 72 h (P<0.05) after cerebral ischemia. Immunohistochemical analyses of VEGF expression revealed that it started to increase at 4 h after brain ischemia in the penumbra, reached a peak at 24 h, and weakened at 72 h. The stimulated VEGF production was also observed in hyperglycemic only group. When hyperglycemia and brain ischemia were combined, the VEGF expression was higher than that in hyperglycemic only group (P<0.05). Compared to normoglycemic ischemic group, no additivity of the effects of hyperglycemia combined with brain ischemia was observed. CONCLUSION: (1) The model of experimental hyperglycemia and cerebral ischemia is replicated successfully by applying the method combined in vivo injection of streptozotocin in the lower primate tree shrew with thrombotic focal cerebral ischemia. (2) This study shows that hyperglycemia aggravates the focal cerebral ischemia damage. (3) Cerebral ischemia and hyperglycemia both can independently up-regulate VEGF expression, but there is no additional increase in VEGF expression when hyperglycemia combined with brain ischemia is applied.