枸杞多糖减轻高血糖加重脑缺血损伤及对Opa1和Drp1表达的影响

发布时间：2018-01-30 18:09

本文关键词： 枸杞多糖高血糖神经保护作用脑缺血再灌注损伤线粒体分裂/融合因子　出处：《宁夏医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的枸杞多糖具有神经保护作用,但其改善高血糖加重脑缺血再灌注损伤的作用知之甚少。本研究探讨糖尿病高血糖加重脑缺血再灌注损伤的机制及枸杞多糖(lycium barbarum polysaccharide,LBP)减轻糖尿病高血糖加重脑缺血再灌注损伤的作用及其可能机制。方法链脲佐菌素(streptozotocin,STZ)建立SD大鼠糖尿病高血糖实验模型。大脑中动脉阻塞(middle cerebral artery occlusion,MCAO)法制备局灶性脑缺血再灌注模型,再灌注24h,72h时。实验分组:(1)正常血糖脑缺血再灌注组(NG);(2)糖尿病高血糖脑缺血再灌注组(HG);(3)糖尿病高血糖脑缺血再灌注枸杞多糖预处理组(LBP);(4)糖尿病高血糖脑缺血再灌注胰岛素预处理组(Insulin)。对比观察大鼠体重、血糖,神经功能,梗死体积,组织病理学、组织化学,视神经萎缩蛋白1(optic atrophy 1,Opa1),动力相关蛋白1(dynamin-related protein1,Drp1)免疫表达。结果 HG组血糖明显高于NG组,HG组体重较NG组明显降低,枸杞多糖预处理组在1周、4周血糖明显低于HG组(P0.05)。再灌注24h,72h,HG组神经功能障碍评分明显高于NG组,枸杞多糖预处理组和胰岛素预处理组神经功能障碍评分明显低于HG组(P0.05)。脑缺血再灌注24小时,HG组梗死体积明显大于NG组,枸杞多糖预处理组和胰岛素预处理组可减小梗死体积(P0.05)。组织病理学和组织化学结果显示,相比NG组,HG组缺血区和半暗带区可见明显增加的固缩、坏死神经元,更明显的间质水肿、神经元变性(P0.05)。相比HG组,枸杞多糖预处理组可减少固缩神经元数量(P0.05)。免疫组化和Western blotting结果表明,相比NG组,HG组可见增多的线粒体分裂因子Drp1表达及减少的线粒体融合因子Opa1表达(P0.05)。相比HG组,缺血再灌注后的枸杞多糖预处理可下调Drp1表达及上调Opa1表达(P0.05)。结论高血糖可加重大脑缺血后再灌注损伤,其机制可能与线粒体分裂增加和线粒体融合降低有关;枸杞多糖可通过促进线粒体融合及降低线粒体分裂,减轻高血糖条件下脑缺血再灌注损伤。
[Abstract]:Objective Lycium barbarum polysaccharide has neuroprotective effect. However, the effect of hyperglycemia on cerebral ischemia-reperfusion injury was not well understood. This study was designed to explore the mechanism of hyperglycemia and the mechanism of LBP. Lycium barbarum polysaccharide. Methods streptozotocin was induced by streptozotocin. Middle cerebral artery occlusion. The focal cerebral ischemia-reperfusion model was established by MCAO method. After 24 hours of reperfusion, the rats were divided into two groups: 1) normal blood glucose cerebral ischemia-reperfusion group. (2) hyperglycemic cerebral ischemia-reperfusion group (HGG); (3) LBPX in diabetic hyperglycemia cerebral ischemia-reperfusion pretreatment group; 4) Insulin in insulin preconditioning group with hyperglycemia, cerebral ischemia and reperfusion. Body weight, blood glucose, nerve function, infarct volume, histopathology and histochemistry were observed. Optic nerve atrophy protein (1) optic atrophy 1 (OPA 1), dynamic related protein (1) dynamin-related protein1. Results the blood glucose in HG group was significantly higher than that in NG group and the body weight in HG group was significantly lower than that in NG group. The blood glucose in HG group was significantly lower than that in HG group (P 0.05), and the neurological dysfunction score in HG group was significantly higher than that in NG group at 24 h or 72 h after reperfusion. The scores of neurological dysfunction in LBP preconditioning group and insulin preconditioning group were significantly lower than those in HG group (P 0.05). The infarct volume in HG group was significantly larger than that in NG group after 24 hours of cerebral ischemia and reperfusion. LBP pretreatment group and insulin pretreatment group can reduce the infarct volume of P0.050.The histopathological and histochemical results showed that compared with NG group. In HG group, pyknosis, necrotic neurons, interstitial edema and degeneration of neurons in ischemic and penumbra regions were significantly increased than those in HG group. The pretreatment group of Lycium barbarum polysaccharides could reduce the number of pyknotic neurons. The results of immunohistochemistry and Western blotting showed that compared with NG group. In HG group, the expression of Mitochondrial mitogen Drp1 and reduced mitochondrial fusion factor Opa1 were increased. The pretreatment of Lycium barbarum polysaccharides after ischemia and reperfusion can down-regulate the expression of Drp1 and up-regulate the expression of Opa1. Conclusion hyperglycemia can aggravate the cerebral ischemia-reperfusion injury. The mechanism may be related to the increase of mitochondrial division and the decrease of mitochondrial fusion. Lycium barbarum polysaccharides can reduce cerebral ischemia-reperfusion injury by promoting mitochondrial fusion and reducing mitochondrial division.
【学位授予单位】：宁夏医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R743.3

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