【背景】帕金森病是一种神经退行性疾病,常伴有胃肠功能障碍等非运动症状。肠道菌群紊乱与肠上皮通透性增强是引起肠道屏障功能障碍的主要因素。饮食限制可改善肠道菌群的构成、维持肠上皮稳态。本文假设隔日禁食对帕金森病模型小鼠肠...【背景】帕金森病是一种神经退行性疾病,常伴有胃肠功能障碍等非运动症状。肠道菌群紊乱与肠上皮通透性增强是引起肠道屏障功能障碍的主要因素。饮食限制可改善肠道菌群的构成、维持肠上皮稳态。本文假设隔日禁食对帕金森病模型小鼠肠道屏障有保护作用,其机制可能与纠正肠道菌群的失调以及促进肠紧密连接蛋白的表达有关。【目的】探究隔日禁食对帕金森病模型小鼠肠道屏障的保护作用及其机制。【方法】32只C57BL/6小鼠随机分成生理盐水+自由饮食组(NS+AL组,n=8)、生理盐水+隔日禁食组(NS+ADF组,n=8)、MPTP+自由饮食组(MPTP+AL组,n=8)、MPTP+隔日禁食组(MPTP+ADF组,n=8)共4组。隔日禁食方案以48h为一个实验周期,前24h采取禁食,后24h采取自由摄食,在第12-14个周期内连续5d给予小鼠腹腔注射1-甲基-4苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine,MPTP)建立帕金森病模型。在隔日禁食17个周期结束后收集小鼠粪便,通过16S r RNA基因高通量测序检测小鼠肠道菌群的变化;小鼠行为学测试后收集其空肠组织,通过HE染色观察肠道病理组织学变化,通过RT-qPCR方法检测AMPK、Occludin、ZO-1的mRNA表达水平(Prkaa1、Ocln、Tjp1),通过Western blotting方法检测ZO-1的蛋白表达水平。【结果】行为学测试结果显示,与NS+AL组相比,MPTP+AL组小鼠运动能力显著下降(P<0.01),而MPTP+ADF组小鼠运动障碍有所改善(P<0.01)。HE染色可见NS+AL组小鼠空肠绒毛结构完整、排列紧密,MPTP+AL组空肠绒毛破碎甚至脱落,而MPTP+ADF组则显示出空肠绒毛相对完整、排列紧密。肠道菌群测序结果显示,MPTP+AL组相较于NS+AL组,肠道菌群的丰度和多样性显著升高(P<0.001),而相较于MPTP+ADF组并无显著变化;各组间小鼠的肠道菌群构成具有显著差异,相对物种丰度在科水平的检测结果显示,与NS+AL组相比,MPTP+AL组艾克曼菌科(Akkermansia展开更多
Objective： To explore the effects of alternate-day-fasting （ADF） therapy combined with Lingguizhugan Decoction （LD）on blood lipid profiles of hyperlipidemic rats. Methods： Rats were randomly assigned into high-f...Objective： To explore the effects of alternate-day-fasting （ADF） therapy combined with Lingguizhugan Decoction （LD）on blood lipid profiles of hyperlipidemic rats. Methods： Rats were randomly assigned into high-fat-diet （HF） group andnormal-diet （ND） group. Hyperlipidemic rats fed with high-fat-diet for 5 weeks were randomly divided into ADF group,alternate-day-fasting with LD （ALG） group and model control （MC） group. The rats in ALG and ADF group weredeprived of food for 24 h every other day for 4 weeks. Rats in ALG group were administrated with LD at fasting day.After 4 weeks of ADF therapy, plasma TC, TG, LDL-c and HDL-c were measured in each group. Expression of miR-143and PPAR-γ protein from adipose was also analyzed. Results： When compared with MC group, after 4 weeks of ADF orcombined ADF and LD therapy, the body weight was evidently reduced in ADF and ALG groups （P = 0.028, P = 0.036by wk 8）. The levels of plasma TC and TG decreased in ADF group and ALG group, which were significantly lower thanthose in MC group （P 〈 0.001, P = 0.045; P 〈 0.001, P = 0.005）. However, the body weight and level of TC and TG inALG group showed non-statistical difference in comparison with ADF group （ALG vs. ADF, P 〉 0.05）. Expression ofmiR-143 and PPAR-γ were higher in MC group than that in NC group （P 〈 0.001）. Compared with MC group,expression of miR-143 and PPAR-γ were significantly decreased in ADF （P = 0.038, P = 0.015） and ALG （P = 0.007, P〈 0.001） groups. When compared with ADF group, expression of miR-143 and PPAR-γ were significantly decreased inALG （P = 0.041, P = 0.046） group. Conclusion： ADF therapy alone not only reduced blood lipids, but also inhibitedmiR-143 and PPAR-γ protein expression in visceral adipose tissue. However, LD couldn’t reduce the levels of bloodlipid profiles more effectively than using ADF alone. Perhaps the effects of LD combined with ADF in the prevention ofhyperlipidemia need further exploration.展开更多
文摘【背景】帕金森病是一种神经退行性疾病,常伴有胃肠功能障碍等非运动症状。肠道菌群紊乱与肠上皮通透性增强是引起肠道屏障功能障碍的主要因素。饮食限制可改善肠道菌群的构成、维持肠上皮稳态。本文假设隔日禁食对帕金森病模型小鼠肠道屏障有保护作用,其机制可能与纠正肠道菌群的失调以及促进肠紧密连接蛋白的表达有关。【目的】探究隔日禁食对帕金森病模型小鼠肠道屏障的保护作用及其机制。【方法】32只C57BL/6小鼠随机分成生理盐水+自由饮食组(NS+AL组,n=8)、生理盐水+隔日禁食组(NS+ADF组,n=8)、MPTP+自由饮食组(MPTP+AL组,n=8)、MPTP+隔日禁食组(MPTP+ADF组,n=8)共4组。隔日禁食方案以48h为一个实验周期,前24h采取禁食,后24h采取自由摄食,在第12-14个周期内连续5d给予小鼠腹腔注射1-甲基-4苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine,MPTP)建立帕金森病模型。在隔日禁食17个周期结束后收集小鼠粪便,通过16S r RNA基因高通量测序检测小鼠肠道菌群的变化;小鼠行为学测试后收集其空肠组织,通过HE染色观察肠道病理组织学变化,通过RT-qPCR方法检测AMPK、Occludin、ZO-1的mRNA表达水平(Prkaa1、Ocln、Tjp1),通过Western blotting方法检测ZO-1的蛋白表达水平。【结果】行为学测试结果显示,与NS+AL组相比,MPTP+AL组小鼠运动能力显著下降(P<0.01),而MPTP+ADF组小鼠运动障碍有所改善(P<0.01)。HE染色可见NS+AL组小鼠空肠绒毛结构完整、排列紧密,MPTP+AL组空肠绒毛破碎甚至脱落,而MPTP+ADF组则显示出空肠绒毛相对完整、排列紧密。肠道菌群测序结果显示,MPTP+AL组相较于NS+AL组,肠道菌群的丰度和多样性显著升高(P<0.001),而相较于MPTP+ADF组并无显著变化;各组间小鼠的肠道菌群构成具有显著差异,相对物种丰度在科水平的检测结果显示,与NS+AL组相比,MPTP+AL组艾克曼菌科(Akkermansia
文摘Objective： To explore the effects of alternate-day-fasting （ADF） therapy combined with Lingguizhugan Decoction （LD）on blood lipid profiles of hyperlipidemic rats. Methods： Rats were randomly assigned into high-fat-diet （HF） group andnormal-diet （ND） group. Hyperlipidemic rats fed with high-fat-diet for 5 weeks were randomly divided into ADF group,alternate-day-fasting with LD （ALG） group and model control （MC） group. The rats in ALG and ADF group weredeprived of food for 24 h every other day for 4 weeks. Rats in ALG group were administrated with LD at fasting day.After 4 weeks of ADF therapy, plasma TC, TG, LDL-c and HDL-c were measured in each group. Expression of miR-143and PPAR-γ protein from adipose was also analyzed. Results： When compared with MC group, after 4 weeks of ADF orcombined ADF and LD therapy, the body weight was evidently reduced in ADF and ALG groups （P = 0.028, P = 0.036by wk 8）. The levels of plasma TC and TG decreased in ADF group and ALG group, which were significantly lower thanthose in MC group （P 〈 0.001, P = 0.045; P 〈 0.001, P = 0.005）. However, the body weight and level of TC and TG inALG group showed non-statistical difference in comparison with ADF group （ALG vs. ADF, P 〉 0.05）. Expression ofmiR-143 and PPAR-γ were higher in MC group than that in NC group （P 〈 0.001）. Compared with MC group,expression of miR-143 and PPAR-γ were significantly decreased in ADF （P = 0.038, P = 0.015） and ALG （P = 0.007, P〈 0.001） groups. When compared with ADF group, expression of miR-143 and PPAR-γ were significantly decreased inALG （P = 0.041, P = 0.046） group. Conclusion： ADF therapy alone not only reduced blood lipids, but also inhibitedmiR-143 and PPAR-γ protein expression in visceral adipose tissue. However, LD couldn’t reduce the levels of bloodlipid profiles more effectively than using ADF alone. Perhaps the effects of LD combined with ADF in the prevention ofhyperlipidemia need further exploration.
