發(fā)布時(shí)間：2018-01-30 18:09

  本文關(guān)鍵詞： 枸杞多糖 高血糖 神經(jīng)保護(hù)作用 腦缺血再灌注損傷 線粒體分裂/融合因子　出處：《寧夏醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的 枸杞多糖具有神經(jīng)保護(hù)作用,但其改善高血糖加重腦缺血再灌注損傷的作用知之甚少。本研究探討糖尿病高血糖加重腦缺血再灌注損傷的機(jī)制及枸杞多糖(lycium barbarum polysaccharide,LBP)減輕糖尿病高血糖加重腦缺血再灌注損傷的作用及其可能機(jī)制。方法 鏈脲佐菌素(streptozotocin,STZ)建立SD大鼠糖尿病高血糖實(shí)驗(yàn)?zāi)Ｐ�。大腦中動(dòng)脈阻塞(middle cerebral artery occlusion,MCAO)法制備局灶性腦缺血再灌注模型,再灌注24h,72h時(shí)。實(shí)驗(yàn)分組:(1)正常血糖腦缺血再灌注組(NG);(2)糖尿病高血糖腦缺血再灌注組(HG);(3)糖尿病高血糖腦缺血再灌注枸杞多糖預(yù)處理組(LBP);(4)糖尿病高血糖腦缺血再灌注胰島素預(yù)處理組(Insulin)。對(duì)比觀察大鼠體重、血糖,神經(jīng)功能,梗死體積,組織病理學(xué)、組織化學(xué),視神經(jīng)萎縮蛋白1(optic atrophy 1,Opa1),動(dòng)力相關(guān)蛋白1(dynamin-related protein1,Drp1)免疫表達(dá)。結(jié)果 HG組血糖明顯高于NG組,HG組體重較NG組明顯降低,枸杞多糖預(yù)處理組在1周、4周血糖明顯低于HG組(P0.05)。再灌注24h,72h,HG組神經(jīng)功能障礙評(píng)分明顯高于NG組,枸杞多糖預(yù)處理組和胰島素預(yù)處理組神經(jīng)功能障礙評(píng)分明顯低于HG組(P0.05)。腦缺血再灌注24小時(shí),HG組梗死體積明顯大于NG組,枸杞多糖預(yù)處理組和胰島素預(yù)處理組可減小梗死體積(P0.05)。組織病理學(xué)和組織化學(xué)結(jié)果顯示,相比NG組,HG組缺血區(qū)和半暗帶區(qū)可見(jiàn)明顯增加的固縮、壞死神經(jīng)元,更明顯的間質(zhì)水腫、神經(jīng)元變性(P0.05)。相比HG組,枸杞多糖預(yù)處理組可減少固縮神經(jīng)元數(shù)量(P0.05)。免疫組化和Western blotting結(jié)果表明,相比NG組,HG組可見(jiàn)增多的線粒體分裂因子Drp1表達(dá)及減少的線粒體融合因子Opa1表達(dá)(P0.05)。相比HG組,缺血再灌注后的枸杞多糖預(yù)處理可下調(diào)Drp1表達(dá)及上調(diào)Opa1表達(dá)(P0.05)。結(jié)論 高血糖可加重大腦缺血后再灌注損傷,其機(jī)制可能與線粒體分裂增加和線粒體融合降低有關(guān);枸杞多糖可通過(guò)促進(jìn)線粒體融合及降低線粒體分裂,減輕高血糖條件下腦缺血再灌注損傷。
[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.
【學(xué)位授予單位】：寧夏醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R743.3

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