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微生物学通报

APP/PS1转基因老年性痴呆模型小鼠肠道甲醛浓度异常升高
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北京市科委科技脑研究计划项目(No. Z161100000216137);国家重点研发计划项目(No. 2016YFC1306300)


Markedly elevated formaldehyde in the cecum of APP/PS1 transgenic mouse model of Alzheimer’s disease
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    摘要:

    【目的】肠道菌群通过“微生物-肠道-脑轴”影响中枢神经系统的功能,同时也与老年性痴呆的发生发展相关,特别是盲肠内微生物菌群的变化更为显著。肠道菌群可以产生和代谢甲醛,而肠道能够迅速吸收甲醛;体内甲醛含量与老年性痴呆病人的认知损害程度呈正相关。因此,本文比较了7月龄APP/PS1转基因老年性痴呆模型小鼠(简称APP/PS1转基因小鼠)与同月龄C57BL/6J野生型小鼠(简称C57BL/6J小鼠)肠道菌群产生甲醛的情况。【方法】取APP/PS1转基因小鼠(n=8)与C57BL/6J小鼠(n=9)的不同肠段(十二指肠、小肠、盲肠、结肠),采用2,4-dinitrophenylhydrazi zne (DNPH)显色偶联高效液相色谱(HPLC coupled with DNPH)测定肠道消化物和肠壁组织的甲醛。【结果】APP/PS1转基因小鼠盲肠消化物内的甲醛含量,较C57BL/6J小鼠存在显著升高(P=0.036);而两者小肠和结肠消化物甲醛含量无显著差别。在两种小鼠之间,小肠壁内甲醛存在差异(P=0.052),而盲肠和结肠壁甲醛含量无显著差异(P>0.05)。【结论】肠道菌群是小鼠体内甲醛的主要来源之一,无论肠道消化物,还是肠道壁组织均为盲肠的甲醛含量最高。这些结果表明,APP/PS1转基因小鼠肠道菌群存在甲醛代谢失调,从而导致其肠道消化物的甲醛含量升高。

    Abstract:

    [Objective] Intestinal microbiota affects the function of central nervous system through the “microbiota-gut-brain axis”. Alzheimer’s disease (AD) is considered being related with the microbiota in the intestines. Concentrations of endogenous formaldehyde are positively correlated to the cognitive impairment of AD inpatients. Therefore, we compared the concentration of intestinal formaldehyde between APP/PS1 transgenic mouse model of Alzheimer’s disease and C57BL/6J wildtype mice. [Methods] Take different sections of duodenum, small intestine, cecum, and colon of APP/PS1 transgenic mice (n=8) and those of C57BL/6J wildtype mice (n=9), respectively. Measure the concentrations of formaldehyde in the digestion contents and intestinal walls with HPLC coupled with 2,4-dinitrophenylhydrazine (DNPH) absorptions. [Results] The levels of the cecum formaldehyde in the digestion contents from APP/PS1 transgenic mice were significantly (P=0.036) higher than those from C57BL/6J wildtype mice, but no significant (P>0.05) difference could be observed in the small intestine and colon. Formaldehyde in walls of duodenum, cecum and colon were not significantly different except for the small intestine. That is, the concentration of formaldehyde was observably elevated in small intestinal wall though the change approached to the significant (P=0.052) different. For APP/PS1 mice, the concentration of formaldehyde in cecum either digestion content or wall exhibited the highest, compared with the other intestinal sections. [Conclusion] Intestinal microbiota is one of the important sources producing formaldehyde. The elevated concentrations of formaldehyde in the cecum digestion contents and small intestinal wall of APP/PS1 transgenic AD mice suggested that dysmetabolism of formaldehyde in the intestinal microbiota may be related to age-related cognitive impairment.

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刘开力,赫英舸,于乐祥,陈瑶,赫荣乔. APP/PS1转基因老年性痴呆模型小鼠肠道甲醛浓度异常升高[J]. 微生物学通报, 2017, 44(8): 1761-1766

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  • 在线发布日期: 2017-08-08
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