Enteric oxalate elimination is induced and oxalate is normalized in a mouse model of primary hyperoxaluria following intestinal colonization with Oxalobacter
Enteric oxalate elimination is induced and oxalate is normalized in a mouse model of primary hyperoxaluria following intestinal colonization with Oxalobacter
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DOI：
10.1152/ajpgi.00434.2010
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发表时间：
2011-03-01
影响因子：
4.5
通讯作者：
Freel, Robert W.
中科院分区：
文献类型：
--
作者：
Hatch, Marguerite;Gjymishka, Altin;Freel, Robert W.
首页--期刊主要分类--期刊细介绍--期刊题录与文摘-期刊详细文摘内容在草酸杆菌肠道定植后的原发性高草酸尿症小鼠模型中，草酸被诱导肠道消除，草酸被正常化。Am J Physiol胃肠病肝生理学300：G461-G469,2011。首次发表于2010年12月16日；doi：10.1152/ajpgi.00434.2010。-之前有研究表明，草酸杆菌在大鼠肠道的定植可以促进肠道草酸的分泌和消除，从而显著减少尿中草酸的排泄(Hatch等人。《国际肾脏病》69：691-698,2006)。本研究的主要目的是利用1型高草酸血症(PH1)的小鼠模型，验证草酸杆菌在小鼠肠道的定植可以增加肠道草酸的分泌，并有效减少与这种遗传病相关的高草酸尿的假设。研究对象为野生型(WT)小鼠和肝丙氨酸乙二酸氨基转移酶(Agxt)缺乏表现为高草酸血症和高草酸尿的小鼠。我们比较了草酸在人工定居和非定居小鼠的隔离短路大肠中的单向和净通量。此外，还测定了血浆和尿草酸。我们的结果表明，盲肠和远端结肠对草酸在草酸杆菌定植的Agxt和WT小鼠肠道中的排泄有显著贡献。在定植的Agxt小鼠中，尿草酸排泄量减少了50%(在WT小鼠观察到的正常范围内)。此外，Agxt小鼠的血浆草酸浓度也正常化(降低50%)。WT小鼠的定植也与显著(高达95%)的尿草酸排泄减少有关。我们得出结论，在PH1小鼠模型中，草酸杆菌对肠道草酸运输的节段特异性影响与其他高草酸血症和高草酸尿动物的血浆草酸和尿草酸排泄正常化有关。
Hatch M, Gjymishka A, Salido EC, Allison MJ, Freel RW. Enteric oxalate elimination is induced and oxalate is normalized in a mouse model of primary hyperoxaluria following intestinal colonization with Oxalobacter. Am J Physiol Gastrointest Liver Physiol 300: G461-G469, 2011. First published December 16, 2010; doi:10.1152/ajpgi.00434.2010.-Oxalobacter colonization of rat intestine was previously shown to promote enteric oxalate secretion and elimination, leading to significant reductions in urinary oxalate excretion (Hatch et al. Kidney Int 69: 691-698, 2006). The main goal of the present study, using a mouse model of primary hyperoxaluria type 1 (PH1), was to test the hypothesis that colonization of the mouse gut by Oxalobacter formigenes could enhance enteric oxalate secretion and effectively reduce the hyperoxaluria associated with this genetic disease. Wild-type (WT) mice and mice deficient in liver alanine-glyoxylate aminotransferase (Agxt) exhibiting hyperoxalemia and hyperoxaluria were used in these studies. We compared the unidirectional and net fluxes of oxalate across isolated, short-circuited large intestine of artificially colonized and noncolonized mice. In addition, plasma and urinary oxalate was determined. Our results demonstrate that the cecum and distal colon contribute significantly to enteric oxalate excretion in Oxalobacter-colonized Agxt and WT mice. In colonized Agxt mice, urinary oxalate excretion was reduced 50% (to within the normal range observed for WT mice). Moreover, plasma oxalate concentrations in Agxt mice were also normalized (reduced 50%). Colonization of WT mice was also associated with marked (up to 95%) reductions in urinary oxalate excretion. We conclude that segment-specific effects of Oxalobacter on intestinal oxalate transport in the PH1 mouse model are associated with a normalization of plasma oxalate and urinary oxalate excretion in otherwise hyperoxalemic and hyperoxaluric animals.