Objective Previous research indicates a link between cognitive impairment and chronic kidney disease(CKD),but the underlying factors are not fully understood.This study aimed to investigate the progression of CKD-indu...Objective Previous research indicates a link between cognitive impairment and chronic kidney disease(CKD),but the underlying factors are not fully understood.This study aimed to investigate the progression of CKD-induced cognitive impairment and the involvement of cognition-related proteins by developing early-and late-stage CKD models in Sprague-Dawley rats.Methods The Morris water maze test and the step-down passive avoidance task were performed to evaluate the cognitive abilities of the rats at 24 weeks after surgery.Histopathologic examinations were conducted to examine renal and hippocampal damage.Real-time PCR,Western blotting analysis,and immunohistochemical staining were carried out to determine the hippocampal expression of brain-derived neurotrophic factor(BDNF),choline acetyltransferase(ChAT),and synaptophysin(SYP).Results Compared with the control rats,the rats with early-stage CKD exhibited mild renal damage,while those with late-stage CKD showed significantly increased serum creatinine levels as well as apparent renal and brain damage.The rats with early-stage CKD also demonstrated significantly impaired learning abilities and memory compared with the control rats,with further deterioration observed in the rats with late-stage CKD.Additionally,we observed a significant downregulation of cognition-related proteins in the hippocampus of rats with early-stage CKD,which was further exacerbated with declining renal function as well as worsening brain and renal damage in rats with late-stage CKD.Conclusion These results suggest the importance of early screening to identify CKD-induced cognitive dysfunction promptly.In addition,the downregulation of cognition-related proteins may play a role in the progression of cognitive dysfunction.展开更多
目的观察当归多糖对阿尔茨海默病(AD)模型大鼠学习记忆、海马β-淀粉样蛋白前体(APP)、β-淀粉样蛋白(Aβ)1-42及血清乙酰胆碱(Ach)、胆碱乙酰转移酶(ChAT)、乙酰胆碱酯酶(AChE)、超氧化物歧化酶(SOD)、丙二醛(MDA)的影响,探讨其防治AD...目的观察当归多糖对阿尔茨海默病(AD)模型大鼠学习记忆、海马β-淀粉样蛋白前体(APP)、β-淀粉样蛋白(Aβ)1-42及血清乙酰胆碱(Ach)、胆碱乙酰转移酶(ChAT)、乙酰胆碱酯酶(AChE)、超氧化物歧化酶(SOD)、丙二醛(MDA)的影响,探讨其防治AD的作用机制。方法 70只SPF级Wistar大鼠经水迷宫学习记忆能力筛选合格后,随机选取10只大鼠(雌雄各半)为假手术组,其余大鼠以脑立体定位注射Aβ25-35复制AD大鼠模型,以水迷宫学习记忆能力筛选造模成功的50只大鼠随机分为模型组、阳性药组和当归多糖低、中、高剂量组,每组10只。模型组和假手术组大鼠给予生理盐水灌胃,各给药组大鼠给予相应药液灌胃,每日给药体积均为2 m L/100 g,连续28 d。给药25~28 d Morris水迷宫测试大鼠学习记忆能力,然后取材检测血清Ach、ChAT、AChE、SOD、MDA及海马APP、Aβ1-42。结果与假手术组比较,模型组大鼠定位航行实验逃避潜伏期明显延长,目标象限滞留时间缩短,空间探索实验首次到达原逃生平台位置潜伏时间延长,穿越原平台位置及目标象限滞留的时间缩短,血清Ach含量与ChAT、SOD活性明显降低,AChE活性及MDA水平明显升高,海马APP、Aβ1-42含量升高,差异均有统计学意义(P<0.05,P<0.01);与模型组比较,各给药组大鼠逃避潜伏期均不同程度缩短,目标象限滞留时间延长,首次到达原逃生平台位置潜伏时间缩短,跨原平台次数增加,血清Ach含量和ChAT、SOD活性升高,AChE活性及MDA水平明降低,海马APP、Aβ1-42含量降低,差异均有统计学意义(P<0.05,P<0.01)。结论当归多糖可能通过改善胆碱能神经递质、提高抗自由基氧化能力及促进Aβ的代谢,改善AD模型大鼠学习记忆能力,对AD有一定的防治作用。展开更多
基金the Youth Fund of the Shanghai Municipal Health Commission(No.20164Y0266).
文摘Objective Previous research indicates a link between cognitive impairment and chronic kidney disease(CKD),but the underlying factors are not fully understood.This study aimed to investigate the progression of CKD-induced cognitive impairment and the involvement of cognition-related proteins by developing early-and late-stage CKD models in Sprague-Dawley rats.Methods The Morris water maze test and the step-down passive avoidance task were performed to evaluate the cognitive abilities of the rats at 24 weeks after surgery.Histopathologic examinations were conducted to examine renal and hippocampal damage.Real-time PCR,Western blotting analysis,and immunohistochemical staining were carried out to determine the hippocampal expression of brain-derived neurotrophic factor(BDNF),choline acetyltransferase(ChAT),and synaptophysin(SYP).Results Compared with the control rats,the rats with early-stage CKD exhibited mild renal damage,while those with late-stage CKD showed significantly increased serum creatinine levels as well as apparent renal and brain damage.The rats with early-stage CKD also demonstrated significantly impaired learning abilities and memory compared with the control rats,with further deterioration observed in the rats with late-stage CKD.Additionally,we observed a significant downregulation of cognition-related proteins in the hippocampus of rats with early-stage CKD,which was further exacerbated with declining renal function as well as worsening brain and renal damage in rats with late-stage CKD.Conclusion These results suggest the importance of early screening to identify CKD-induced cognitive dysfunction promptly.In addition,the downregulation of cognition-related proteins may play a role in the progression of cognitive dysfunction.
文摘目的观察当归多糖对阿尔茨海默病(AD)模型大鼠学习记忆、海马β-淀粉样蛋白前体(APP)、β-淀粉样蛋白(Aβ)1-42及血清乙酰胆碱(Ach)、胆碱乙酰转移酶(ChAT)、乙酰胆碱酯酶(AChE)、超氧化物歧化酶(SOD)、丙二醛(MDA)的影响,探讨其防治AD的作用机制。方法 70只SPF级Wistar大鼠经水迷宫学习记忆能力筛选合格后,随机选取10只大鼠(雌雄各半)为假手术组,其余大鼠以脑立体定位注射Aβ25-35复制AD大鼠模型,以水迷宫学习记忆能力筛选造模成功的50只大鼠随机分为模型组、阳性药组和当归多糖低、中、高剂量组,每组10只。模型组和假手术组大鼠给予生理盐水灌胃,各给药组大鼠给予相应药液灌胃,每日给药体积均为2 m L/100 g,连续28 d。给药25~28 d Morris水迷宫测试大鼠学习记忆能力,然后取材检测血清Ach、ChAT、AChE、SOD、MDA及海马APP、Aβ1-42。结果与假手术组比较,模型组大鼠定位航行实验逃避潜伏期明显延长,目标象限滞留时间缩短,空间探索实验首次到达原逃生平台位置潜伏时间延长,穿越原平台位置及目标象限滞留的时间缩短,血清Ach含量与ChAT、SOD活性明显降低,AChE活性及MDA水平明显升高,海马APP、Aβ1-42含量升高,差异均有统计学意义(P<0.05,P<0.01);与模型组比较,各给药组大鼠逃避潜伏期均不同程度缩短,目标象限滞留时间延长,首次到达原逃生平台位置潜伏时间缩短,跨原平台次数增加,血清Ach含量和ChAT、SOD活性升高,AChE活性及MDA水平明降低,海马APP、Aβ1-42含量降低,差异均有统计学意义(P<0.05,P<0.01)。结论当归多糖可能通过改善胆碱能神经递质、提高抗自由基氧化能力及促进Aβ的代谢,改善AD模型大鼠学习记忆能力,对AD有一定的防治作用。
