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锌氧化物纳米载芦丁可改善糖尿病大鼠非酒精性脂肪肝疾病并伴有胰岛素抵抗 通过调控 PI3K/AKT/FoxO1 信号通路。

Luteolin loaded on zinc oxide nanoparticles ameliorates non-alcoholic fatty liver disease associated with insulin resistance in diabetic rats regulation of PI3K/AKT/FoxO1 pathway.

机构信息

Radiation Biology Research, National Center for Radiation Research and Technology, 68892Egyptian Atomic Energy Authority, Cairo, Egypt.

出版信息

Int J Immunopathol Pharmacol. 2022 Jan-Dec;36:3946320221137435. doi: 10.1177/03946320221137435.

DOI:10.1177/03946320221137435
PMID:36319192
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9630902/
Abstract

OBJECTIVE

Non-alcoholic fatty liver disease (NAFLD) is a worldwide health problem with high prevalence and morbidity associated with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), and dyslipidemia. Nano-formulation of luteolin with Zn oxide in the form of Lut/ZnO NPs may improve the anti-diabetic property of each alone and ameliorate the insulin resistance thus management of NAFLD. This study aimed to measure the efficiency of Lut/ZnO NPs against insulin resistance coupled with NAFLD and T2DM.

METHODS

A diabetic rat model with NAFLD was induced by a high-fat diet and streptozotocin (30 mg/kg I.P). Serum diabetogenic markers levels, lipid profile, and activity of liver enzymes were measured beside liver oxidative stress markers. Moreover, the hepatic expressions of PI3K/AKT/FoxO1/SERBP1c as well as heme oxygenase-1 were measured beside the histopathological examination.

RESULTS

Lut/ZnO NPs treatment effectively reduced hyperglycemia, hyperinsulinemia, and ameliorated insulin resistance. Additionally, Lut/ZnO NPs improved the hepatic functions, the antioxidant system, and reduced the oxidative stress markers. Furthermore, the lipid load in the liver, as well as the circulating TG and TC, was minified the suppression of lipogenesis and gluconeogenesis. Moreover, Lut/ZnO NPs activated the PI3K/AKT signaling pathway, hence inactivating FoxO1, therefore enhancing the hepatic cells' insulin sensitivity.

CONCLUSION

Lut/ZnO NPs have a hepatoprotective effect and may relieve the progression of NAFLD by alleviating insulin resistance, ameliorating the antioxidant status, and regulating the insulin signal pathway.

摘要

目的

非酒精性脂肪性肝病(NAFLD)是一个全球性的健康问题,其患病率和发病率较高,与肥胖、胰岛素抵抗、2 型糖尿病(T2DM)和血脂异常有关。叶黄素与氧化锌以 Lut/ZnO NPs 的形式形成纳米制剂,可能会提高其各自的抗糖尿病特性,并改善胰岛素抵抗,从而对 NAFLD 进行管理。本研究旨在测量 Lut/ZnO NPs 对抗伴有胰岛素抵抗的非酒精性脂肪性肝病和 2 型糖尿病的效率。

方法

通过高脂肪饮食和链脲佐菌素(30mg/kg,腹腔注射)诱导非酒精性脂肪性肝病伴糖尿病大鼠模型。测量血清致糖尿病标志物水平、脂质谱和肝酶活性,以及肝氧化应激标志物。此外,还测量了 PI3K/AKT/FoxO1/SERBP1c 以及血红素加氧酶-1 的肝表达,以及组织病理学检查。

结果

Lut/ZnO NPs 治疗可有效降低血糖、胰岛素血症,并改善胰岛素抵抗。此外,Lut/ZnO NPs 改善了肝功能、抗氧化系统,并降低了氧化应激标志物。此外,肝脏中的脂质负荷,以及循环 TG 和 TC,通过抑制脂肪生成和糖异生而减少。此外,Lut/ZnO NPs 激活了 PI3K/AKT 信号通路,从而使 FoxO1 失活,从而增强了肝细胞的胰岛素敏感性。

结论

Lut/ZnO NPs 具有肝保护作用,通过减轻胰岛素抵抗、改善抗氧化状态和调节胰岛素信号通路,可能缓解 NAFLD 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/9630902/fbf8a55f42eb/10.1177_03946320221137435-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/9630902/b628b4fa511b/10.1177_03946320221137435-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/9630902/dac1e2ae8f0a/10.1177_03946320221137435-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/9630902/4274d2647336/10.1177_03946320221137435-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/9630902/bb04e5d08d35/10.1177_03946320221137435-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/9630902/9da1488c947a/10.1177_03946320221137435-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/9630902/b5ba63a61578/10.1177_03946320221137435-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/9630902/fbf8a55f42eb/10.1177_03946320221137435-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/9630902/b628b4fa511b/10.1177_03946320221137435-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/9630902/dac1e2ae8f0a/10.1177_03946320221137435-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/9630902/4274d2647336/10.1177_03946320221137435-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/9630902/bb04e5d08d35/10.1177_03946320221137435-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/9630902/9da1488c947a/10.1177_03946320221137435-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/9630902/b5ba63a61578/10.1177_03946320221137435-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/9630902/fbf8a55f42eb/10.1177_03946320221137435-fig7.jpg

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