Exendin-4，一种胰高血糖素样肽-1 受体激动剂，可下调非酒精性脂肪性肝炎大鼠模型肝内晚期糖基化终产物受体。
Exendin-4, a glucagon-like peptide-1 receptor agonist downregulates hepatic receptor for advanced glycation end products in non-alcoholic steatohepatitis rat model.
机构信息
a Physiology Department, Faculty of Medicine , Benha University , Benha , Egypt.
b Biochemistry Department, Faculty of Medicine , Benha University , Benha , Egypt.
出版信息
Arch Physiol Biochem. 2018 Feb;124(1):10-17. doi: 10.1080/13813455.2017.1348362. Epub 2017 Jul 11.
CONTEXT
Exendin-4, a glucagon-like peptide-1 receptor agonist has been shown to have curative effects on hepatic steatosis in murine models.
OBJECTIVE
The present study aimed to elucidate the effect of Exendin-4 on hepatic receptor for advanced glycation end products (RAGE) mRNA expression in non-alcoholic steatohepatitis (NASH) rat model induced by high-fat diet.
METHODS
NASH was induced by high-fat diet intake, and Exendin-4 was given in two different doses. After 12 weeks, liver enzyme levels, hepatic triglycerides, antioxidant enzymes and malondialdehyde (MDA) levels, and mRNA RAGE was detected using RT-PCR.
RESULTS
Exendin-4 in high dose reduced significantly liver enzymes activity, hepatic triglycerides, MDA levels and hepatic mRNA RAGE expression levels with significantly higher antioxidant enzymes activity.
CONCLUSIONS
Our results give further insights into the mechanisms underlying the curative role of Exendin-4 in NASH, suggesting that interference with RAGE may be a useful therapeutic approach to NASH.
背景
胰高血糖素样肽-1 受体激动剂 Exendin-4 已被证明对小鼠模型中的肝脂肪变性具有治疗作用。
目的
本研究旨在阐明 Exendin-4 对高脂肪饮食诱导的非酒精性脂肪性肝炎（NASH）大鼠模型中肝晚期糖基化终产物受体（RAGE）mRNA 表达的影响。
方法
采用高脂肪饮食摄入诱导 NASH，给予两种不同剂量的 Exendin-4。12 周后，使用 RT-PCR 检测肝酶水平、肝甘油三酯、抗氧化酶和丙二醛（MDA）水平以及 RAGE mRNA。
结果
高剂量的 Exendin-4 显著降低了肝酶活性、肝甘油三酯、MDA 水平和肝 mRNA RAGE 表达水平，同时显著提高了抗氧化酶活性。
结论
我们的结果进一步深入了解了 Exendin-4 在 NASH 中的治疗作用机制，表明干扰 RAGE 可能是治疗 NASH 的一种有效方法。
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