耐力训练和荨麻叶提取物对 STZ 诱导糖尿病大鼠 IDO1-KYN-AHR 通路稳态的协同作用及肝毒性的抑制作用。

Synergistic effect of endurance training and nettle leaf extract on the IDO1-KYN-AHR pathway homeostasis and inhibiting of liver toxicity in rats with STZ-induced diabetes.

机构信息

Department of Sport Sciences, Faculty of Humanities, Semnan University, Semnan, Iran.

Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Front Endocrinol (Lausanne). 2023 May 26;14:1071424. doi: 10.3389/fendo.2023.1071424. eCollection 2023.

DOI:10.3389/fendo.2023.1071424

PMID:37305057

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10251405/

Abstract

INTRODUCTION

Diabetes adversely affects a number of hepatic molecular pathways, including the kynurenine (KYN) pathway. KYN is produced by indoleamine 2,3-dioxygenase (IDO) and activates the aryl hydrocarbon receptor (AHR). This study evaluated the effect of endurance training (EndTr) and nettle leaf extract (NLE) on the IDO1-KYN-AHR pathway in the livers of rats with streptozotocin-induced diabetes.

METHODS

We divided 48 rats into six groups: controls (Ct), treated with EndTr (EndTr), diabetes-induced (D), D treated with NLE (D + NLE), D treated with EndTr (D + EnTr), and D treated with EndTr and NLE (D + EndTr + NLE). EndTr, D + EnTr, and D + EndTr + NLE groups were subjected to training with running on treadmill for 8 weeks, 5 days per week, 25 min in first session to 59 min at last session with intensity of 55% to 65% VO2max. Using real-time PCR gene (, , and ) expressions and ELISA, malondialdehyde (MDA) and protein (IDO1, AHR, and CYP1A1) levels were determined in the liver samples.

RESULTS

A significant three-way interaction of exercise, nettle, and diabetes was observed on the all variables (P< 0.001). In particular, significant increases in blood glucose level (BGL), in gene and protein expression, and in MDA and KYN levels were observed in the liver samples of the D group versus the Ct group (P< 0.05). BGL and liver MDA levels were significantly lower in the D + EndTr and D + NLE groups than that in the D group. However, the D + EndTr + NLE group showed a more significant decrease in these factors (P< 0.05). In addition, liver KYN levels were significantly lower in the EndTr group compared with that in the Ct group as well as in the D + EndTr + NLE and D + EndTr groups compared with that in the D groups (P< 0.05). Whereas both the EndTr and D + NLE groups showed lower expression and AHR level compared with the Ct and D groups, respectively (P< 0.05), the D + EndTr + NLE group showed a higher significant reduction in the AHR level than the D group (P< 0.05). The expression and IDO1 level significantly decreased only in the D + EndTr + NLE group compared to that in the D group (P< 0.05).

CONCLUSION

Overall, this study showed that the combination of EndTr and NLE may synergistically restore the imbalanced IDO1-KYN-AHR pathway in diabetic liver.

摘要

简介

糖尿病会对许多肝内分子途径产生不利影响，包括犬尿氨酸（KYN）途径。犬尿氨酸由吲哚胺 2,3-双加氧酶（IDO）产生，并激活芳香烃受体（AHR）。本研究评估了耐力训练（EndTr）和荨麻叶提取物（NLE）对链脲佐菌素诱导糖尿病大鼠肝脏中 IDO1-KYN-AHR 途径的影响。

方法

我们将 48 只大鼠分为六组：对照组（Ct）、经 EndTr 处理（EndTr）、糖尿病诱导组（D）、经 NLE 处理的糖尿病组（D + NLE）、经 EndTr 处理的糖尿病组（D + EnTr）和经 EndTr 和 NLE 处理的糖尿病组（D + EndTr + NLE）。EndTr、D + EnTr 和 D + EndTr + NLE 组通过在跑步机上跑步进行训练，每周 5 天，每次 25 分钟，最后一次训练强度为 55%至 65%VO2max。使用实时 PCR 基因（、和）表达和 ELISA，测定肝组织样本中的丙二醛（MDA）和蛋白质（IDO1、AHR 和 CYP1A1）水平。

结果

在所有变量上，运动、荨麻和糖尿病的显著三向相互作用（P<0.001）。特别是，与 Ct 组相比，D 组的血糖水平（BGL）、基因和蛋白质表达以及 MDA 和 KYN 水平均显著升高（P<0.05）。D + EndTr 和 D + NLE 组的 BGL 和肝 MDA 水平明显低于 D 组。然而，D + EndTr + NLE 组的这些因素下降更为显著（P<0.05）。此外，与 Ct 组以及 D + EndTr + NLE 和 D + EndTr 组相比，EndTr 组的肝 KYN 水平显著降低（P<0.05）。与 Ct 和 D 组相比，EndTr 和 D + NLE 组的表达和 AHR 水平均降低（P<0.05），而 D + EndTr + NLE 组的 AHR 水平较 D 组显著降低（P<0.05）。与 D 组相比，只有 D + EndTr + NLE 组的表达和 IDO1 水平显著降低（P<0.05）。