在慢性肝性脑病(HE)的大鼠模型中,大鼠器官形态的改变影响三羧酸(TCA)循环代谢产物和谷氨酰胺-谷氨酸(Gln-Glu)循环代谢产物的平衡,即α-酮戊二酸(αKG)和α-酮戊二酸(αKGM),以及与之相关的酶,ω-酰胺酶(ωA)和谷氨酰胺转氨酶(GTK)。该大鼠模型是由于动物将肝毒素硫代乙酰胺(TAA)以0.4g/L的浓度添加到饮用水中2-22周的结果而获得的。对照组(n=26)和TAA诱导的(n=55)大鼠每组由11个队列组成。对照组由2-4只大鼠组成,TAA诱导的队列由4-7人组成。每两周,血浆样本,肝脏,肾,和脑组织取自下一组大鼠(共320个样本)。实验结束时,在大鼠器官中观察到不可逆的形态学变化:动物的重量减少了〜45%,肾脏的重量高达5%,大脑高达约20%,肝脏的重量增加到约20%。分析显示:(i)脑组织中ωA和GTK的活性降低,肾脏,和慢性HE大鼠的肝脏(分别为~3、40和65%和~10、60和70%,分别);和(ii)Gln-Glu循环代谢物含量出现显著失衡,αKG,和αKGM。表明慢性HE大鼠血浆和器官组织中αKG水平的~1.5-12倍的增加伴随着同步,αKGM水平降低约1.2-2.5倍。获得的数据表明,在慢性HE条件下,Gln-Glu循环在调节大鼠能量代谢方面具有重要作用。注意力集中在αKG/αKGM比率的重要性上,它可以作为诊断HE发展程度的潜在标志物。
In the example of a rat model with chronic
hepatoencephalopathy (HE), changes in the organ morphology of rats affect the balance of metabolites of the tricarboxylic acid (TCA) cycle and metabolites of the glutamine-glutamate (Gln-Glu) cycle, namely α-ketoglutarate (αKG) and α-ketoglutaramate (αKGM), as well as the enzymes associated with them, ω-amidase (ωA) and glutamine transaminase (GTK). This model of rats was obtained as a result of 2-22 weeks of consumption by animals of hepatotoxin thioacetamide (TAA) added to drinking water at a concentration of 0.4 g/L. The control (n = 26) and TAA-induced (n = 55) groups of rats consisted of 11 cohorts each. The control cohorts consisted of 2-4 rats, and the TAA-induced cohorts consisted of 4-7 individuals. Every two weeks, samples of blood plasma, liver, kidney, and brain tissues were taken from the next cohort of rats (a total of 320 samples). By the end of the experiment, irreversible morphological changes were observed in the organs of rats: the weight of the animals was reduced up to ~45%, the weight of the kidneys up to 5%, the brain up to ~20%, and the weight of the liver increased up to ~20%. The analysis revealed: (i) a decrease in the activity of ωA and GTK in the tissues of the brain, kidneys, and liver of rats with chronic HE (by ~3, 40, and 65% and ~10, 60, and 70%, respectively); and (ii) the appearance of a significant imbalance in the content of metabolites of the Gln-Glu cycle, αKG, and αKGM. It is indicative that a ~1.5-12-fold increase in the level of αKG in the blood plasma and tissues of the organs of rats with chronic HE was accompanied by a synchronous, ~1.2-2.5-fold decrease in the level of αKGM. The data obtained indicate an essential involvement of the Gln-Glu cycle in the regulation of energy metabolism in rats under conditions of chronic HE. Attention is focused on the significance of the αKG/αKGM ratio, which can act as a potential marker for diagnosing the degree of HE development.