Cano N, Catelloni F, Fontaine E, Novaretti R, di Costanzo-Dufetel J, Reynier J P, Leverve X M
Laboratoire de Thérapeutique, Biologie, Université Joseph Fourier, Grenoble, France.
Kidney Int. 1995 Jun;47(6):1522-7. doi: 10.1038/ki.1995.215.
Metabolic changes due to chronic renal failure (CRF) were studied in isolated liver cells. In 14 CRF and 14 sham-operated rats, liver cells were isolated by the Berry and Friend method and incubated with various substrates in order to study gluconeogenesis, ureagenesis, ketogenesis, oxygen consumption as well as cytosolic and mitochondrial adenine nucleotide content. CRF rat hepatocytes exhibited a 25% to 45% decrease in gluconeogenesis and ureagenesis (P < 0.05) from all the tested substrates (lactate plus pyruvate, fructose, glycerol, dihydroxyacetone, alanine and glutamine for gluconeogenesis and alanine, glutamine, ammonia and ammonia plus ornithine for ureagenesis), while endogenous rates were unaffected. CRF did not alter ketone body production (acetoacetate and beta-hydroxybutyrate) from oleate or octanoate. In the presence of either oleate, lactate plus pyruvate or ammonia, oxygen uptake as well as cytosolic and mitochondrial total adenine nucleotides were unaffected by CRF, while the mitochondrial ATP/ADP ratio decreased (P < 0.001). Thus, this study of hepatocyte intermediary metabolism during CRF showed an alteration of only gluconeogenesis and ureagenesis pathways. Moreover, the association of normal oxygen uptake together with decreased mitochondrial ATP/ADP ratio suggest a possible increase in hepatocyte ATP demand during uremia.
在分离的肝细胞中研究了慢性肾衰竭（CRF）引起的代谢变化。选取14只CRF大鼠和14只假手术大鼠，采用Berry和Friend方法分离肝细胞，并与各种底物一起孵育，以研究糖异生、尿素生成、酮体生成、耗氧量以及胞质和线粒体腺嘌呤核苷酸含量。CRF大鼠肝细胞从所有测试底物（用于糖异生的乳酸加丙酮酸、果糖、甘油、二羟基丙酮、丙氨酸和谷氨酰胺，以及用于尿素生成的丙氨酸、谷氨酰胺、氨和氨加鸟氨酸）进行糖异生和尿素生成的能力降低了25%至45%（P<0.05），而内源性速率未受影响。CRF并未改变油酸或辛酸生成酮体（乙酰乙酸和β-羟基丁酸）的能力。在存在油酸、乳酸加丙酮酸或氨的情况下，CRF对氧摄取以及胞质和线粒体总腺嘌呤核苷酸没有影响，但线粒体ATP/ADP比值降低（P<0.001）。因此，这项关于CRF期间肝细胞中间代谢的研究表明，只有糖异生和尿素生成途径发生了改变。此外，正常的氧摄取与降低的线粒体ATP/ADP比值相结合，提示尿毒症期间肝细胞对ATP的需求可能增加。
