PROTEINURIA, NOT ALTERED ALBUMIN METABOLISM, AFFECTS HYPERLIPIDEMIA IN THE NEPHROTIC RAT
PROTEINURIA, NOT ALTERED ALBUMIN METABOLISM, AFFECTS HYPERLIPIDEMIA IN THE NEPHROTIC RAT
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DOI：
10.1172/jci114750
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发表时间：
1990-08-01
影响因子：
15.9
通讯作者：
KAYSEN, GA
中科院分区：
文献类型：
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作者：
DAVIES, RW;STAPRANS, I;KAYSEN, GA
先前已经确定肾病性高脂血症的特征在于脂质合成增加和脂蛋白去除缺陷。这些缺陷与白蛋白代谢改变之间的关系尚不确定。一种假设是肝脏脂肪生成与白蛋白合成平行增加。为了验证这一假设，通过将膳食蛋白质增加至40%（HPN），在喂食8.5%蛋白质膳食（LPN）的肾病大鼠中增加白蛋白合成。依那普利（HPE）在一半喂食40%蛋白质的大鼠中调节蛋白尿。HPN和HPE的白蛋白合成是相同的，但与HPN相比，HPE的蛋白尿减少，血清胆固醇和甘油三酯（TG）也减少。为了检查在无蛋白尿的情况下血清白蛋白对脂质清除的影响，在长濑无白蛋白血症大鼠（NAR）中测定了乳糜微粒（CM）和VLDL的血浆清除率，发现与正常SD大鼠无差异。在NAR和SD大鼠中诱导蛋白尿时，两组CM和VLDL清除率均出现严重和相同的缺陷，两组血脂水平升高的程度相似。高脂血症和脂蛋白从循环中的清除缺陷都与白蛋白合成或血清白蛋白浓度无关，但至少部分是由蛋白尿引起的。与非肾病对照组相比，肾病动物中肝素后脂蛋白脂酶（LPL）活性轻微降低，但最引人注目的发现是与SD大鼠相比，正常NAR中肝素后LPL活性显著降低（P < 0.001），表明LPL活性降低与肾病大鼠中CM和VLDL清除率降低无关。
It has been established previously that nephrotic hyperlipidemia is characterized by both an increase in lipid synthesis and a defect in removal of lipoproteins. The relationship between these defects and altered albumin metabolism is uncertain. One hypothesis is that hepatic lipogenesis increases in parallel with albumin synthesis. To test this hypothesis, albumin synthesis was increased in nephrotic rats fed an 8.5% protein diet (LPN) by increasing dietary protein to 40% (HPN). Proteinuria was modulated in half of the rats fed 40% protein by enalapril (HPE). Albumin synthesis was the same in both HPN and HPE, but proteinuria was reduced in HPE compared to HPN, and so were serum cholesterol and triglycerides (TG). To examine the effect of serum albumin on lipid clearance in the absence of proteinuria, plasma clearance of chylomicrons (CM) and VLDL was measured in Nagase analbuminemic rats (NAR) and found to be no different than in normal SD rats. When proteinuria was induced in NAR and in SD rats, a severe and identical defect in both CM and VLDL clearance was acquried in both groups and blood lipid levels were increased to a similar degree in both groups. Neither hyperlipidemia nor defective removal of lipoproteins from the circulation are linked to albumin synthesis or serum albumin concentration but result, at least in part, from proteinuria. Postheparin lipoprotein lipase (LPL) activity was reduced slightly in nephrotic animals compared to nonnephrotic controls, but the most striking finding was a highly significant decrease in postheparin LPL activity in normal NAR compared to SD rats (P < 0.001), suggesting that reduced LPL activity is not responsible for reduced clearance of CM and VLDL in nephrotic rats.