消旋卡多曲对老年大鼠脑内淀粉样蛋白水平的影响

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目的:探讨消旋卡多曲对老年大鼠脑内β-淀粉样蛋白的水平的影响。方法30只老年 SD大鼠随机分为空白对照组,消旋卡多曲高剂量组,消旋卡多曲低剂量组。消旋卡多曲高、低剂量组,连续4 w,1次/d,给予不同剂量消旋卡多曲灌胃,空白对照组灌以等量20% PEG400溶液。灌胃结束后,酶联免疫吸附法( ELISA)测定大脑及外周血中Aβ1~40、Aβ1~42和脑啡肽酶( NEP)的含量,病理检查观察大脑海马区的病理改变情况。结果 ELISA结果显示,与空白对照组相比,消旋卡多曲各剂量组脑组织Aβ1~40、Aβ1~42水平较对照组显著升高(P<0.05),NEP水平有下降的趋势,仅高剂量组差异有显著性( P<0.05);空白对照组与消旋卡多曲各剂量组在外周血液中 Aβ1~40、Aβ1~42和 NEP 的含量均无明显差异( P>0.05);病理检查发现消旋卡多曲各剂量组大脑海马CA3区及齿状回神经元较空白对照组明显减少。结论超量应用消旋卡多曲可促使脑组织中Aβ水平升高,有增加老年大鼠AD发病风险的可能。“,”Objective To evaluate the risk of Alzheimer′s disease which be used Racecadotril to effect the level of beta-amyliod in the brain of aged rats.Methods 30 mices were randomly divided into Racecadotril high , low dose treatment and control groups.Rats were given gastric perfusion of Racecadotril in Racecadotril high , low dose treatment groups , and were perfused to same volume 20%PEG400 in control group.Levels of Aβ1~40 ,Aβ1~42 , NEP in brain and peripheral blood were analyzed by ELISA and the effect of Racecadotril on mice brain was investigated by H&E staining.Results Aβ1~40 ,Aβ1~42 levels were significantly increased in the brain of low and high dose of Racecadotril groups compared with the control group ( P<0.05 ).The level of NEP had decreasing tendency , there was significant difference between high dose of Racecadotril group and control group ( P<0.05 ).But all rats had minor changes of peripheral blood.H&E staining showed neuronal loss and a proliferation of microglia were detected in hippocampal formation.Conclusions Racecadotril overdose could in-crease the risk of Alzheimer′disease in aged rats by upregulating Aβ1~40 , Aβ1~42 levels of brain tissue.
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