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生物活性脂质在慢性营养不良大鼠的肾脏中发生改变:这与普遍存在的肾病进展有任何相关性吗?

Bioactive lipids are altered in the kidney of chronic undernourished rats: is there any correlation with the progression of prevalent nephropathies?

机构信息

Instituto de Biofísica Carlos Chagas Filho - CCS, UFRJ, Rio de Janeiro, RJ, Brazil.

Programa de Pós-Graduação em Biomedicina Translacional, Universidade do Grande Rio, Duque de Caxias, RJ, Brazil.

出版信息

Lipids Health Dis. 2017 Dec 16;16(1):245. doi: 10.1186/s12944-017-0634-z.

DOI:10.1186/s12944-017-0634-z
PMID:29246161
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5732436/
Abstract

BACKGROUND

Undernutrition during childhood leads to chronic diseases in adult life including hypertension, diabetes and chronic kidney disease. Here we explore the hypothesis that physiological alterations in the bioactive lipids pattern within kidney tissue might be involved in the progression of chronic kidney disease.

METHODS

Membrane fractions from kidney homogenates of undernourished rats (RBD) were submitted to lipid extraction and analysis by thin layer chromatography and cholesterol determination.

RESULTS

Kidneys from RBD rats had 25% lower cholesterol content, which disturb membrane microdomains, affecting Ca homeostasis and the enzymes responsible for important lipid mediators such as phosphatidylinositol-4 kinase, sphingosine kinase, diacylglicerol kinase and phospholipase A. We observed a decrease in phosphatidylinositol(4)-phosphate (8.8 ± 0.9 vs. 3.6 ± 0.7 pmol.mg.mim), and an increase in phosphatidic acid (2.2 ± 0.8 vs. 3.8 ± 1.3 pmol.mg.mim), being these lipid mediators involved in the regulation of key renal functions. Ceramide levels are augmented in kidney tissue from RBD rats (18.7 ± 1.4 vs. 21.7 ± 1.5 fmol.mg.min) indicating an ongoing renal lesion.

CONCLUSION

Results point to an imbalance in the bioactive lipid generation with further consequences to key events related to kidney function, thus contributing to the establishment of chronic kidney disease.

摘要

背景

儿童时期的营养不良会导致成年后患高血压、糖尿病和慢性肾病等慢性疾病。在这里,我们探讨了这样一种假设,即在肾脏组织内生物活性脂质模式的生理改变可能与慢性肾病的进展有关。

方法

对营养不良大鼠(RBD)的肾脏匀浆的膜部分进行薄层层析和胆固醇测定的脂质提取和分析。

结果

RBD 大鼠的肾脏胆固醇含量低 25%,这会扰乱膜微区,影响钙平衡以及对重要脂质介质如磷脂酰肌醇-4 激酶、鞘氨醇激酶、二酰基甘油激酶和磷脂酶 A 负责的酶。我们观察到磷脂酰肌醇(4)-磷酸(8.8±0.9 对 3.6±0.7 pmol.mg.mim)减少,而磷脂酸(2.2±0.8 对 3.8±1.3 pmol.mg.mim)增加,这些脂质介质参与了关键肾脏功能的调节。RBD 大鼠肾脏组织中的神经酰胺水平升高(18.7±1.4 对 21.7±1.5 fmol.mg.min),表明存在持续的肾脏损伤。

结论

结果表明生物活性脂质生成的不平衡,对与肾功能相关的关键事件产生进一步的影响,从而有助于慢性肾病的发生。

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