三尖杉酯碱通过胰岛素相关 IRS1-GLUT2 通路对糖尿病大鼠肝脏的保护作用:生化、分子、组织病理学和免疫组织化学研究

Meizhi Li, Shiqing Li, Shanshan Jiang, Weihong Li
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引用次数: 0

摘要

背景:糖尿病会大大增加发病率和死亡率,导致心血管疾病、肾衰竭和失明等并发症。目的:本研究旨在探讨三尖杉酯碱(TRIG)通过抗氧化、抗炎和与胰岛素相关的 IRS1-GLUT2 通路对糖尿病大鼠肝脏的保护作用。研究方法在这项实验研究中,60 只雄性 Wistar 大鼠(n = 10/组)被随机分为六组:健康组(HEL)、接受 1500 和 3000 mg/kg TRIG 治疗的健康大鼠、糖尿病组(D)和接受 1500 和 3000 mg/kg TRIG 治疗的糖尿病大鼠(D+ TRIG)。通过血清生化指标,如胰岛素、肿瘤坏死因子-α (TNF-α)、白细胞介素-6 (IL-6)、游离脂肪酸 (FFA)、一氧化氮和脂肪连素水平,评估了 TRIG 对诱发糖尿病大鼠的影响。还测定了肝脏碳水化合物代谢酶(肝葡萄糖激酶、葡萄糖-6-磷酸酶、糖原和葡萄糖-6-磷酸脱氢酶)的活性。此外,还使用实时 PCR 和 Western 印迹技术分别分析了与碳水化合物/脂质代谢相关的基因和蛋白质的表达水平,包括过氧化物酶体增殖激活受体γ(PPARg)、葡萄糖转运体 2(GLUT2)、胰岛素受体底物 1(IRS1)、甾醇调节元件结合蛋白 1c(SREBP-1c)。肝脏切片采用 H&E 染色和针对 p53 蛋白的免疫组化技术进行检测。结果显示结果表明,3000 毫克/千克 TRIG 能够通过抑制炎症通路和提高抗氧化酶的活性来抑制 TNF-α、IL-6 和 FFA。通过调节 IRS1/ GLUT2- SREBP-1c/ PPARg 途径,TRIG 治疗可调节血清中的胰岛素、脂肪连素和肝脏碳水化合物代谢酶水平以及糖原含量。结论这些结果证明,TRIG 有可能保护糖尿病患者的肝脏器官免受氧化损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Hepatoprotective Effect of Trigonelline in Diabetic Rat Through Insulin-related IRS1-GLUT2 Pathway: A Biochemical, Molecular, Histopathological, and Immunohistochemical 
Study
Background: Diabetes significantly increases morbidity and mortality rates, causing complications such as cardiovascular disease, kidney failure, and blindness. Purpose: The aim of this study was to investigate the hepatoprotective effects of trigonelline (TRIG) in diabetic rats through the antioxidative, anti-inflammatory, and insulin-related IRS1-GLUT2 pathway. Methods: In this experimental investigation, sixty male Wistar rats (n = 10/group) were randomly divided into six groups: a healthy group (HEL), healthy rats treated with 1500 and 3000 mg/kg of TRIG, a diabetic (D), and diabetic rats treated with 1500 and 3000 mg/kg of TRIG (D+ TRIG). The effects of TRIG on rats with induced diabetes were evaluated by serum biochemical parameters, such as insulin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), free fatty acids (FFA), nitric oxide, and adiponectin levels. The activities of hepatic carbohydrate metabolic enzymes (hepatic glucokinase, glucose 6-phosphatase, glycogen, and glucose-6-phosphate dehydrogenase) were also measured. Furthermore, the expression levels of genes and proteins associated with carbohydrate/lipid metabolism, including peroxisome proliferator-activated receptor gamma (PPARg), glucose transporter 2 (GLUT2), insulin receptor substrate 1 (IRS1), sterol regulatory element-binding protein 1c (SREBP-1c) were analyzed using real-time PCR and western blotting techniques, respectively. Liver sections were examined using H&E staining and immunohistochemistry targeting the p53 protein. Results: The results showed that 3000 mg/kg TRIG was able to suppress TNF-α, IL-6, and FFA by inhibiting inflammatory pathways along with increasing the activity of antioxidant enzymes. TRIG treatment regulated serum levels of insulin, adiponectin, and hepatic carbohydrate metabolic enzymes as well as glycogen content by regulation of the IRS1/ GLUT2- SREBP-1c/ PPARg pathway. Conclusion: These results provide evidence that TRIG has the potential to protect liver organs from oxidative damage in diabetic patients.
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