In female rats, ethylene glycol treatment elevates protein expression of hepatic and renal oxalate transporter sat-1 (Slc26a1) without inducing hyperoxaluria
In female rats, ethylene glycol treatment elevates protein expression of hepatic and renal oxalate transporter sat-1 (Slc26a1) without inducing hyperoxaluria
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DOI：
10.3325/cmj.2015.56.447
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发表时间：
2015-10-01
影响因子：
1.9
通讯作者：
Sabolic, Ivan
中科院分区：
文献类型：
--
作者：
Breljak, Davorka;Brzica, Hrvoje;Sabolic, Ivan
目的探讨乙二醇（EG）诱导的高尿酸大鼠模型中肝、肾草酸转运蛋白sat-1（Slc 26 a1）表达的性别依赖性变化。通过血浆、尿液和组织中的生化参数确认草酸尿状态。免疫细胞化学（蛋白质）和/或真实的时间反转录聚合酶链反应（mRNA）检测sat-1和草酸合成限速酶乙醇脱氢酶1（Adh 1）和羟酸氧化酶1（Hao 1）的表达。（单位：μ mol/L;平均值+/-标准差）血浆（59.7 ± 27.2 vs 12.9 ± 4.1，P < 0.001）和尿液（3716 +/- 1726 vs 241 +/- 204，P < 0.001）草酸水平，草酸盐晶体比对照组更丰富，而肝和肾sat-1蛋白和mRNA表达在这些组之间没有显著差异。与对照组相比，EG处理的雌性动物具有显著更高的（μ mol/L）血清草酸水平（18.8 +/- 2.9 vs 11.6 +/- 4.9，P < 0.001），尿草酸盐水平不变，低草酸盐结晶，并且表达量显著高于（相对荧光单位）（1.59 +/- 0.61 vs 0.56 +/- 0.39，P = 0.006）和肾脏（1.77 +/- 0.42 vs 0.69 +/- 0.27，P < 0.001）sat-1蛋白，而非mRNA。Adh 1和Hao 1的mRNA表达均以雌性为主，但均不受EG处理的影响。结论EG处理的雌性大鼠肝、肾组织中草酸转运蛋白sat-1的表达增加，对高尿酸血症和草酸盐尿石症具有保护作用。
Aim To investigate whether the sex-dependent expression of hepatic and renal oxalate transporter sat-1 (Slc26a1) changes in a rat model of ethylene glycol (EG)-induced hyperoxaluria.Methods Rats were given tap water (12 males and 12 females; controls) or EG (12 males and 12 females; 0.75% v/v in tap water) for one month. Oxaluric state was confirmed by biochemical parameters in blood plasma, urine, and tissues. Expression of sat-1 and rate-limiting enzymes of oxalate synthesis, alcohol dehydrogenase 1 (Adh1) and hydroxy-acid oxidase 1 (Hao1), was determined by immunocytochemistry (protein) and/or real time reverse transcription polymerase chain reaction (mRNA).Results EG-treated males had significantly higher (in mu mol/L; mean +/- standard deviation) plasma (59.7 +/- 27.2 vs 12.9 +/- 4.1, P < 0.001) and urine (3716 +/- 1726 vs 241 +/- 204, P < 0.001) oxalate levels, and more abundant oxalate crystaluria than controls, while the liver and kidney sat-1 protein and mRNA expression did not differ significantly between these groups. EG-treated females, in comparison with controls had significantly higher (in mu mol/L) serum oxalate levels (18.8 +/- 2.9 vs 11.6 +/- 4.9, P < 0.001), unchanged urine oxalate levels, low oxalate crystaluria, and significantly higher expression (in relative fluorescence units) of the liver (1.59 +/- 0.61 vs 0.56 +/- 0.39, P = 0.006) and kidney (1.77 +/- 0.42 vs 0.69 +/- 0.27, P < 0.001) sat-1 protein, but not mRNA. The mRNA expression of Adh1 was female-dominant and that of Hao1 male-dominant, but both were unaffected by EG treatment.Conclusions An increased expression of hepatic and renal oxalate transporting protein sat-1 in EG-treated female rats could protect from hyperoxaluria and oxalate urolithiasis.