李旭蕊,李 剑,李岩鹏,马志超,李灿灿,曹 宏.卡巴拉汀对阿尔茨海默病模型小鼠肠道菌群及认知功能的影响[J].,2020,(20):3827-3831 |
卡巴拉汀对阿尔茨海默病模型小鼠肠道菌群及认知功能的影响 |
Effect of Rivastigmine on Intestinal Flora and Cognitive Function in Mice with Alzheimer's Disease |
投稿时间:2020-03-03 修订日期:2020-03-27 |
DOI:10.13241/j.cnki.pmb.2020.20.005 |
中文关键词: 阿尔茨海默病 模型 小鼠 认知功能 卡巴拉汀 肠道菌群 |
英文关键词: Rivastigmine Alzheimer's disease Intestinal flora Cognitive function |
基金项目:国家自然科学基金项目(81870544);河北省医学科学研究项目(20190215) |
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中文摘要: |
摘要 目的:探究卡巴拉汀对阿尔茨海默病模型小鼠肠道菌群及认知功能的影响。方法:将所选取的大鼠随机分组,第一组,模型组(MO组):该组大鼠制作阿尔茨海默病大鼠模型;第二组,假手术组(SS组):该组大鼠在颅脑处做切口后不做任何处理;第三组,治疗组(TR组):该组大鼠制作阿尔茨海默病模型后给予卡巴拉汀进行治疗,每组5只。通过避暗实验、qRT-PCR法、流式细胞仪、水迷宫行为测试、Western blot法等方法分析三组小鼠被动学习记忆能力、空间学习记忆能力、脑细胞凋亡情况、肠道菌群分布情况、TNF-α、IL-6的蛋白含量的差异性来探究卡巴拉汀对阿尔茨海默病模型小鼠肠道菌群及认知功能的影响。结果:由表可知,SS组、TR组、MO组小鼠潜伏期分别为158.39±84.26、127.54±71.84、65.82±21.03 s,错误次数分别为0.75±0.14、1.21±0.35、1.79±0.67,SS组小鼠潜伏期最长,错误次数最少,MO组则与之相反,TR组与MO组相比较,TR组被动学习记忆能力显著比MO组优良(P<0.05)。实验结果显示,SS组小鼠潜伏期时间最长,错误次数最少,MO组小鼠潜伏期时间最短,错误次数最多,TR组与MO组相比较,TR组空间学习记忆能力显著比MO组优良(P<0.05)。检测结果显示,SS组、TR组、MO组小鼠脑细胞凋亡率分别为13.59 %、43.68 %、89.38 %。SS组小鼠脑细胞凋亡数量最少,MO组小鼠脑细胞大量凋亡,MO组与TR组、SS组相比较细胞凋亡率显著下降,TR组与MO组相比较,TR组小鼠脑细胞凋亡数量显著比MO组少(均P<0.05)。qRT-PCR检测结果显示,SS组、TR组、MO组小鼠肠道菌群分布有显著差异,SS组小鼠肠道内双歧杆菌、乳酸杆菌数量最多,大肠杆菌数量最少,MO组小鼠肠道细菌与之相反,MO组与TR组相比较,TR组小鼠肠道菌群分布优于MO组(均P<0.05)。通过Western blot法,对SS组、TR组、MO组小鼠脑细胞内的TNF-α、IL-6蛋白进行免疫印迹,灰度显示,SS组的TNF-α、IL-6蛋白含量最低,MO组蛋白含量最高,MO组和SS组、TR组相比较,脑细胞中TNF-α、IL-6蛋白表达水平显著上升,TR组与SS组相比较,TR组显著比SS组高(均P<0.05)。结论:卡巴拉汀对阿尔茨海默病模型小鼠有显著治疗作用,能够对小鼠的认知功能、肠道菌群有改善效果。 |
英文摘要: |
ABSTRACT Objective: To explore the effect of carbamastatin on the intestinal flora and cognitive function of Alzheimer's disease model mice. Methods: Randomly select the selected rats, the first group, the model group (MO group): this group of rats make Alzheimer's disease rat model; the second group, the sham operation group (SS group): this group Rats did not do any treatment after making an incision in the craniocerebral group; the third group, the treatment group (TR group): the rats in this group were treated with carbamastatin after making Alzheimer's disease model, 5 rats in each group. The three groups of mice were analyzed for passive learning and memory, spatial learning and memory, brain cell apoptosis, and intestinal flora distribution through dark avoidance experiments, qRT-PCR method, flow cytometry, water maze behavior test, Western blot method, etc. Situation, differences in protein content of TNF-α and IL-6 to explore the effect of carbamastatin on the intestinal flora and cognitive function of Alzheimer's disease model mice. Results: From the table, the latency of mice in SS group, TR group, and MO group were 158.39±84.26, 127.54±71.84, 65.82±21.03 s, and the number of errors were 0.75±0.14, 1.21±0.35, 1.79±0.67, SS group. The mice had the longest incubation period and the least number of errors, while the MO group had the opposite. Compared with the MO group, the TR group had significantly better passive learning and memory abilities than the MO group (P<0.05). The experimental results showed that the mice in the SS group had the longest incubation period and the fewest errors, and the mice in the MO group had the shortest incubation period and the most errors. Compared with the MO group, the TR group had significantly better spatial learning and memory ability than the MO group <0.05). The test results showed that the brain cell apoptosis rates in the SS group, TR group, and MO group were 13.59%, 43.68%, and 89.38%, respectively. The number of brain cells in the SS group was the least, and the brain cells in the MO group were largely apoptotic. Compared with the TR group and the SS group, the apoptosis rate of the MO group was significantly reduced, and the TR group was compared with the MO group and the TR group. The number of brain cell apoptosis was significantly less than that in the MO group (both P<0.05). The results of qRT-PCR showed that there were significant differences in the distribution of intestinal flora in mice in SS group, TR group, and MO group. The amount of bifidobacteria and lactobacilli in the intestine of SS group was the largest, and the number of E. coli was the smallest. In contrast to intestinal bacteria, compared with the TR group, the distribution of intestinal flora in the TR group was better than that in the MO group (all P<0.05). Western blotting was used to immunoblot the TNF-α and IL-6 proteins in the brain cells of the SS group, the TR group and the MO group. The gray level showed that the SS group had the lowest TNF-α and IL-6 protein content. The protein content of MO group was the highest. Compared with SS group and TR group, the expression levels of TNF-α and IL-6 protein in brain group of MO group were significantly increased. Compared with SS group, TR group was significantly higher than that of SS group (all P<0.05). Conclusion: Kapalatin has a significant therapeutic effect on Alzheimer's disease model mice and can improve the cognitive function and intestinal flora of mice. |
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