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首页> 外文期刊>International Journal of Molecular Sciences >12-Lipoxygenase Inhibition on Microalbuminuria in Type-1 and Type-2 Diabetes Is Associated with Changes of Glomerular Angiotensin II Type 1 Receptor Related to Insulin Resistance
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12-Lipoxygenase Inhibition on Microalbuminuria in Type-1 and Type-2 Diabetes Is Associated with Changes of Glomerular Angiotensin II Type 1 Receptor Related to Insulin Resistance

机译：12-脂氧合酶对1型和2型糖尿病微白蛋白尿的抑制作用与与胰岛素抵抗相关的肾小球血管紧张素II 1型受体的变化有关

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(1) Background: 12-lipoxygenase (12-LO) is involved in the development of diabetic nephropathy (DN). In the present study, we investigated whether 12-LO inhibition may ameliorate type-2 DN (T2DN) by interfering with insulin resistance (IR); (2) Methods: Rat glomerular mesangial cells, glomeruli and skeletal muscles were isolated and used in this study. Kidney histological changes were confirmed by periodic-acid Schiff staining; mRNA expression was detected by competitive reverse transcription polymerase chain reaction; and the protein level was determined by Western blot and the enzyme-linked immunosorbent assay, respectively; (3) Results: The inhibition of 12-LO attenuated microalbuminuria (MAU) increases in type-2 diabetic rats, but not in type-1 diabetic rats. Infusion of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) significantly increased the expression of angiotensin II (Ang II) and Ang II type 1 receptor (AT1R), but decreased the expression of AT1R-associated protein (ATRAP) in rat glomeruli, compared to the control. An in vitro study revealed that both 12(S)-HETE and insulin upregulated AT1R expression in rat mesangial cells. In the presence of p38 mitogen-activated protein kinase (MAPK) inhibitor, SB202190, the 12(S)-HETE-induced ATRAP reduction was significantly abolished. Interestingly, 12-LO inhibition did not influence AT1R expression in type-1 diabetic rats, but significantly abolished the increased AT1R and Ang II expression in glomeruli of type-2 diabetic rats. Furthermore, the inhibition of 12-LO significantly corrected impaired insulin sensitivity and fast serum insulin level, as well as the p-AMP-activated protein kinase (AMPK) reduction in skeletal muscle of type-2 diabetic rats; (4) Conclusion: The inhibition of 12-LO potentially ameliorated MAU by preventing IR through the downregulation of glomerular AT1R expression in T2DN.
机译：（1）背景：12-脂加氧酶（12-LO）参与糖尿病性肾病（DN）的发展。在本研究中，我们研究了12-LO抑制是否可以通过干扰胰岛素抵抗（IR）来改善2型DN（T2DN）。 （2）方法：分离大鼠肾小球系膜细胞，肾小球和骨骼肌，用于本研究。肾脏组织学改变通过高碘酸希夫（Schiff）染色证实;通过竞争性逆转录聚合酶链反应检测mRNA表达。蛋白质水平分别通过蛋白质印迹法和酶联免疫吸附法测定。 （3）结果：在2型糖尿病大鼠中12-LO减毒微蛋白尿（MAU）的抑制增加，但在1型糖尿病大鼠中没有。输注12（S）-羟基二十碳四烯酸（12（S）-HETE）显着增加血管紧张素II（Ang II）和Ang II 1型受体（AT1R）的表达，但降低AT1R相关蛋白（ATRAP）的表达与对照相比，在大鼠肾小球中。一项体外研究表明，12（S）-HETE和胰岛素均可上调大鼠系膜细胞中AT1R的表达。在存在p38丝裂原活化蛋白激酶（MAPK）抑制剂SB202190的情况下，12（S）-HETE诱导的ATRAP降低被显着消除。有趣的是，12-LO的抑制并不会影响1型糖尿病大鼠的AT1R表达，但是却消除了2型糖尿病大鼠肾小球AT1R和Ang II表达的增加。此外，对12-LO的抑制可显着纠正2型糖尿病大鼠骨骼肌中胰岛素敏感性受损和血清胰岛素水平过快，以及p-AMP活化蛋白激酶（AMPK）的降低; （4）结论：通过下调T2DN中肾小球AT1R表达来防止IR，抑制12-LO可能会改善MAU。

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