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外源性物质代谢中糖尿病大鼠CYP3A4表达的研究

Investigation of the Expression of CYP3A4 in Diabetic Rats in Xenobiotic Metabolism.

作者信息

Güven Naile Merve, Karaömerlioğlu İrem, Arıoğlu İnan Ebru, Can Eke Benay

机构信息

Ankara University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Ankara, Türkiye.

Ankara University, Graduate School of Health Sciences, Ankara, Türkiye.

出版信息

Turk J Pharm Sci. 2024 Mar 25;21(1):81-86. doi: 10.4274/tjps.galenos.2023.87450.

DOI:10.4274/tjps.galenos.2023.87450
PMID:38529568
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10982886/
Abstract

OBJECTIVES

This study investigated the impact of a high-fat diet streptozotocin (STZ)-induced diabetes and dapagliflozin treatment on hepatic protein expression of CYP3A4.

MATERIALS AND METHODS

In our study, 34 male Sprague-Dawley rats were randomly divided into four groups: Control, high-fat diet and STZ-induced diabetes, dapagliflozin-treated control, and dapagliflozin-treated diabetes. In the microsomes obtained from the livers of these rats, the protein expression levels of CYP3A4 were determined by Western blotting.

RESULTS

Hepatic CYP3A4 protein expression levels in the control group treated with dapagliflozin were significantly decreased compared with those in the control group. In addition, hepatic CYP3A4 protein expression levels were decreased in dapagliflozin-treated diabetic Sprague-Dawley rats compared with those in both control and diabetic group rats, but the difference between the groups was not statistically significant.

CONCLUSION

According to these two results, the use of dapagliflozin inhibited hepatic CYP3A4 protein expression.

摘要

目的

本研究调查了高脂饮食联合链脲佐菌素(STZ)诱导的糖尿病以及达格列净治疗对细胞色素P450 3A4(CYP3A4)肝脏蛋白表达的影响。

材料与方法

在我们的研究中,34只雄性Sprague-Dawley大鼠被随机分为四组:对照组、高脂饮食联合STZ诱导糖尿病组、达格列净治疗对照组以及达格列净治疗糖尿病组。在从这些大鼠肝脏获取的微粒体中,通过蛋白质免疫印迹法测定CYP3A4的蛋白表达水平。

结果

与对照组相比,接受达格列净治疗的对照组大鼠肝脏中CYP3A4蛋白表达水平显著降低。此外,与对照组和糖尿病组大鼠相比,接受达格列净治疗的糖尿病Sprague-Dawley大鼠肝脏中CYP3A4蛋白表达水平降低,但组间差异无统计学意义。

结论

根据这两个结果,使用达格列净可抑制肝脏CYP3A4蛋白表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df08/10982886/9324510e176f/TJPS-21-81-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df08/10982886/3a38a7939f3f/TJPS-21-81-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df08/10982886/9324510e176f/TJPS-21-81-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df08/10982886/3a38a7939f3f/TJPS-21-81-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df08/10982886/9324510e176f/TJPS-21-81-g2.jpg

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本文引用的文献

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Molecules. 2022 Jun 16;27(12):3873. doi: 10.3390/molecules27123873.
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Effects of dapagliflozin in combination with insulin on cytochrome P450 activities in a diabetes type 1 rat model.达格列净联合胰岛素对 1 型糖尿病大鼠细胞色素 P450 活性的影响。
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Chronic Inflammatory Status Observed in Patients with Type 2 Diabetes Induces Modulation of Cytochrome P450 Expression and Activity.
在 2 型糖尿病患者中观察到的慢性炎症状态会引起细胞色素 P450 表达和活性的调节。
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Lipophilic Metabolic Efficiency (LipMetE) and Drug Efficiency Indices to Explore the Metabolic Properties of the Substrates of Selected Cytochrome P450 Isoforms.亲脂性代谢效率(LipMetE)和药物效率指数以探索选定细胞色素P450同工酶底物的代谢特性。
ACS Omega. 2019 Dec 30;5(1):179-188. doi: 10.1021/acsomega.9b02344. eCollection 2020 Jan 14.
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Evaluating the impact of type 2 diabetes mellitus on CYP450 metabolic activities: protocol for a case-control pharmacokinetic study.评估2型糖尿病对CYP450代谢活性的影响:一项病例对照药代动力学研究方案
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A practical guide for induction of type-2 diabetes in rat: Incorporating a high-fat diet and streptozotocin.一种实用的诱导大鼠 2 型糖尿病的方法:结合高脂肪饮食和链脲佐菌素。
Biomed Pharmacother. 2017 Nov;95:605-613. doi: 10.1016/j.biopha.2017.08.098. Epub 2017 Sep 4.
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Expression of Cytochrome P450s in the Liver of Rats Administered with Socheongryong-tang, a Traditional Herbal Formula.传统草药配方芍姜龙汤给药大鼠肝脏中细胞色素P450s的表达
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Hepatic expression of cytochrome P450 in Zucker diabetic fatty rats.细胞色素P450在Zucker糖尿病脂肪大鼠中的肝脏表达
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