Shafrir E
Department of Biochemistry, Hadassah University Hospital, Jerusalem, Israel.
Isr J Med Sci. 1996 Jun;32(6):390-7.
Triamcinolone or triiodothyronine (T3) was administered to rats with nephrosis induced by aminonucleoside of puromycin and to control nontreated rats. Triamcinolone produced hyperglycemia, hyperinsulinemia and liver glycogen deposition in control rats and to a lesser extent in nephrotic rats. Triamcinolone treatment did not affect plasma protein and albumin levels but increased the level of plasma triglycerides and cholesterol in the very low density lipoprotein (VLDL) and LDL but not high density lipoprotein fractions. The exacerbation of hyperlipoproteinemia was attributed both to increase hepatic lipid synthesis and delayed removal, since it was associated with the induction of hepatic acetyl-CoA carboxylase, the regulatory enzyme of lipogenesis, as well as with marked suppression of adipose tissue lipoprotein lipase (LPL). The hepatic lipase activity was found to be elevated in nephrotic rats but was suppressed by triamcinolone treatment, indicating a reduced capacity of VLDL to LDL conversion. T3 treatment resulted in serum glucose and insulin increases similar to triamcinolone, but more moderate in nephrotic vs. control rats, and in marked reduction in liver glycogen content. Plasma protein levels were not affected, but contrary to control rats, T3 treatment produced an elevation in serum triglycerides and cholesterol in nephrotic rats. The activity of several hepatic lipogenic enzymes, including acetyl-CoA carboxylase, was markedly elevated, as was the activity of gluconeogenic enzymes. Thus, the hyperlipoproteinemia on T3 treatment appeared to be mainly due to predomination of lipid synthesis over removal, since the activities of enzymes responsible for plasma lipid disposal, adipose tissue LPL and hepatic lipase were enhanced both in control and nephrotic rats. It is remarkable that both T3 and triamcinolone induce the lipogenic enzymes and apolipoproteins in the liver of nephrotic rats, already pronouncedly stimulated to replace the excreted plasma proteins. Thus, the nephrotic liver is able to respond to hormonal stimulation with further specific protein and lipid synthesis. It is also pertinent that the recovery from immunosuppressive treatment of human nephrosis, developing on an immune background, may result in more impressive amelioration of proteinuria and hypoproteinemia than of hyperlipoproteinemia because of the lipidemic effect of glucocorticoids.
将曲安奈德或三碘甲状腺原氨酸（T3）给予由嘌呤霉素氨基核苷诱导肾病的大鼠以及未治疗的对照大鼠。曲安奈德在对照大鼠中产生高血糖、高胰岛素血症和肝糖原沉积，在肾病大鼠中程度较轻。曲安奈德治疗不影响血浆蛋白和白蛋白水平，但增加了极低密度脂蛋白（VLDL）和低密度脂蛋白（LDL）而非高密度脂蛋白部分中的血浆甘油三酯和胆固醇水平。高脂血症的加重归因于肝脏脂质合成增加和清除延迟，因为这与肝脏脂肪酸合成的调节酶乙酰辅酶A羧化酶的诱导以及脂肪组织脂蛋白脂肪酶（LPL）的显著抑制有关。发现肾病大鼠的肝脂肪酶活性升高，但曲安奈德治疗可抑制该活性，表明VLDL向LDL转化的能力降低。T3治疗导致血清葡萄糖和胰岛素升高，与曲安奈德相似，但肾病大鼠与对照大鼠相比更为适度，且肝糖原含量显著降低。血浆蛋白水平未受影响，但与对照大鼠相反，T3治疗使肾病大鼠的血清甘油三酯和胆固醇升高。包括乙酰辅酶A羧化酶在内的几种肝脏脂肪生成酶的活性显著升高，糖异生酶的活性也升高。因此，T3治疗引起的高脂血症似乎主要是由于脂质合成超过清除，因为负责血浆脂质清除的酶、脂肪组织LPL和肝脂肪酶的活性在对照大鼠和肾病大鼠中均增强。值得注意的是，T3和曲安奈德均可诱导肾病大鼠肝脏中的脂肪生成酶和载脂蛋白，而肝脏已因排泄血浆蛋白而受到明显刺激。因此，肾病肝脏能够对激素刺激做出反应，进一步进行特定的蛋白质和脂质合成。同样相关的是，在免疫背景下发生的人类肾病经免疫抑制治疗后恢复时，由于糖皮质激素的脂血症作用，蛋白尿和低蛋白血症的改善可能比高脂血症更为显著。
