【作者】 王菊；

【导师】 杨世杰；

【作者基本信息】 吉林大学 ， 药理学， 2009， 硕士

【摘要】 亚血红素多肽(DhHP-6)是以抗坏血酸过氧化物和微酶的结构为依据合成的一种含亚血红素多肽的六肽衍生物,作为一种过氧化物酶,其具有很强的抗氧化能力,可抑制和阻断氧化损伤的发生。本研究以手术方法制备脑出血及脑缺血模型来探讨亚血红素多肽对于脑出血后及脑缺血的保护作用。实验一,利用大鼠脑立体定位仪,向大鼠脑内注入自体血制备大鼠实验性脑出血模型。观察DhHP-6对大鼠脑出血后3天的脑保护作用。结果表明:DhHP-6可明显抑制大鼠脑出血后脑组织中一氧化氮(NO)的升高,并能明显提高脑组织超氧化物歧化酶(SOD)活性,降低丙二醛(MDA)含量,同时能减轻大鼠的神经功能障碍和脑组织的病理损害。实验二,用丝线结扎大鼠双侧颈总动脉制备大鼠急性不完全脑缺血模型。结果表明:DhHP-6可明显抑制大鼠不完全脑缺血术后脑组织中一氧化氮(NO)的升高,并可明显提高脑组织超氧化物歧化酶(SOD)活性,降低丙二醛(MDA)含量,同时能减轻脑组织的病理损害。实验结果表明,亚血红素多肽对实验性脑出血后及不完全脑缺血具有脑保护作用,其作用机制可能为:DhHP-6增加SOD活性,发挥抗自由基作用,减少MDA生成,降低NO毒性,保护神经细胞膜的完整性,改善脑神经功能。更多还原

【Abstract】 Cerebrovascular disease(CVD)is a devastating clinical condition,which severely do harm to human healthy.Both case-fatality rate and Mutilation rate are high.The significance of the peroxidases is in the prevention and therapy of the diseases caused by free radicals, In spite of the therapeutical potential of natural peroxidases,it is severely limited by its source,difficult refinement,instability,molecular mass and other factors;thus enzyme mimetics of peroxidases are desirable. DhHP-6 is enzyme mimetics of peroxidases made by the method of mimic enzym.In our study,to investigate the protective effects of DhHP-6 on intracerebral hemorrhage and ischemic in rats. The firt model of experimental intracerebral hemorrhage was induced in rats through infusion of 50 ul of fresh autologous blood drawn from caudal artery into the caudate uncleus.The changes behavior were observed.Histopathological change of rat brain subjected,Plasma SOD,MDA and NO,as well as brain tissue SOD,MDA and NO levels,were determined.We made intracerebral hemorrhage model in rats to study the effects of DhHP-6 on neurocyte morphology changes and neurological scale. DhHP-6(1.0mg/kg,0.3mg/kg,0.1mg/kg)can reduced neurological scores(P<0.001、P<0.001、P<0.05), NO and MDA generation,decrease SOD activity After intracerebral hemorrhage. DhHP-6 significantly increased SOD content in plasma(P<0.05)and brain tissu(P<0.01,P<0.05)decreased MDA content in plasma(P<0.01, P<0.05)and brain tissue(P<0.01)as well as in plasma(P<0.05)and brain tissue(P<0.05,P<0.05)NO levels.The second model of experimental, Through setting up incomplete cerebral ischemia. the effects of DhHP-6 on the level of SOD,MDA,NO,CK,LDH both in the brain tissue and serum of rats. At the same time,samples were taken to store in the fixation liquid for HE.In our study,DhHP-6(1.0mg/kg)gnificantly increased SOD content in plasma(P<0.01)and brain tissu(P<0.01)decreased MDA content in plasm(P<0.01 ,P<0.01,P<0.05)and brain tissue(P<0.01,P<0.05)as well as in plasma(P<0.05)and brain tissue(P<0.05)CK and LDH levels.DhHP-6 could obviously decrease the content of MDA and could increase the activity of SOD both in brain tissue and serum; .This indicated that DhHP-6 could increase the anti-oxidation activity of the enzyme, enhance the ability of removing free radicals and reduce the free radical from ischemia-reperfusion,so that it improve function of brain. The results of the experiment also demonstrated that DhHP-6 could strickingly reduce the content of NO in brain tissue,which showed that NaoxinKang Injection could ease the harm of NO.The results of the experiment showed that DhHP-6 could significantly reduce the content of CK and LDH, wich indicates that DhHP-6 could relieve the damageand protect the integrity of cellular membrane.更多还原