PD98059对高血糖加重大鼠全脑缺血再灌注神经细胞损伤的影响

Effect of PD98059 on hyperglycemia-exaggerated cerebral ischemic damage

①目的探讨PD98059在高血糖加重大鼠脑缺血再灌注损伤中的作用。②方法将健康雄性SD大鼠40只分为正常组、全脑缺血再灌注组(IR)、糖尿病+全脑缺血再灌注组(DCI)和糖尿病+全脑缺血再灌注+PD98059抑制剂组(PD),采用链脲佐菌素腹腔注射制作糖尿病大鼠模型,用4-VO法建立全脑缺血再灌注模型。PD组于缺血前20min经尾静脉注入PD98059。采用HE染色观察神经细胞形态变化、采用神经功能学检测表,观察大鼠精神状态、部分感觉和运动能力。③结果与IR组比较,DCI组光镜下神经元数目减少,结构疏松,神经元细胞存活密度降低,神经功能评分低于IR组(P<0.05);与DCI组比较,PD组光镜下细胞周围大量空泡,几乎看不到正常神经细胞,神经元细胞存活密度降低,神经功能评分低于DCI组(P<0.05)。④结论高血糖可加重大鼠全脑缺血再灌注神经细胞损伤;PD98059进一步加重神经细胞的损伤。

Objective To investigate whether PD98059 was involved in mediating hyperglycemia -exaggerated cerebral is- chemic damage. Methods Seventy healthy male SD rats were into control group,isehemia/reperfusion group （IR） ,Diabetes eereb- ralisehemia group （DCI） , PD98059 prevented diabetes cerebral ischemia group （PD）. Hyperglycemia model was made by injection of streptozocin through abdomen and global cerebral ischemia/reperfusion model was produced by 4 - VOmethod. Reperfusion were per- formed after20 min. inject PD98059 from rat tailg vein before cerebral ischemia. The changes of neuron morphous were observed with HE staining. Nerve function deteetion, study the psychosis, part sensation and movement ability of mice. Results Compared to IR group, DCI group under the light microscope, Neuronal ceils decrease in number, the structure is loose, density of survival neurons decreased, the function score of neurological is lower than IR group（ P 〈 0.05 ） ; Compared to DCI group, PD group the edema surrounded is seriously, there is a big mount of vacuoles under light microscope, it is hardly to see normal nerve cell, density of survival neurons decreased, the function score of neurological is lower than DCI group（ P 〈 0.05）. Conclusion Cerebral damage aggravated by hyperglycemia in experimental brain ischemia rats ; The PI398059 may be play some role of inducing poor outcomes with preischemic hyerglycemia.