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运动和荨麻提取物改善链脲佐菌素诱导的糖尿病大鼠的线粒体功能以及心肌细胞核呼吸因子2和过氧化物酶体增殖物激活受体γ共激活因子1α的表达。

Exercise and Urtica Dioica extract ameliorate mitochondrial function and the expression of cardiac muscle Nuclear Respiratory Factor 2 and Peroxisome proliferator-activated receptor Gamma Coactivator 1-alpha in STZ-induced diabetic rats.

作者信息

Seyydi Seyyedeh Masoumeh, Tofighi Asghar, Rahmati Masoud, Tolouei Azar Javad

机构信息

Department of Exercise Physiology and Corrective Movements, Faculty of Sports Sciences, Urmia University, Urmia, Iran.

Department of Exercise Physiology and Corrective Movements, Faculty of Sports Sciences, Urmia University, Urmia, Iran.

出版信息

Gene. 2022 May 15;822:146351. doi: 10.1016/j.gene.2022.146351. Epub 2022 Feb 19.

Abstract

INTRODUCTION

Diabetes mellitus can affect and disrupt the levels of PGC1α and NRF2 proteins in the mitochondrial biogenesis pathway. Considering the anti-diabetic properties of Urtica Dioica extract and exercise, this study aimed to investigate the beneficial effects of Urtica Dioica extract and endurance activity on PGC1α and NRF2 protein levels in the streptozotocin-induced diabetic rat heart tissue.

MATERIALS AND METHODS

58 male Wistar rats were divided into five groups (N = 12) including: healthy control (HC), diabetes control (DC), diabetes Urtica Dioica (D-UD), diabetes exercise training (DT), and diabetes exercise training Urtica Dioica (DT-UD). Diabetes was induced intraperitoneally by STZ (45 mg/kg) injection. Two weeks after the induction of diabetes, the rats were stimulated to carry out the exercise (moderate intensity/5day/week) and the gavage of UD extract (50 mg/kg/day) was administered to the rats for six weeks. In this study, the western blotting method was used to measure the levels of PGC1α and NRF2 proteins. Moreover, cardiography was used to evaluate the functional parameters of the heart (ejection fraction & fractional shortening). Finally, the bioluminescence and ELISA methods were used to determine the content of adenosine triphosphate and citrate synthase.

RESULTS

The cardiac function parameters, the mitochondrial ATP and the CS content in DC group mice were impaired in comparison with the other study groups and showed a decreasing trend (P < 0.001). The treatment with EX + UD extract was able to minimize the rate of these disorders and acted as a protector of mitochondrial function. There were significant differences in the expression levels of NRF2 (F = 17.7, P = 0.001) and PGC-1α (F = 43.7, P = 0.001) mitochondrial proteins among the different groups. The levels of these proteins were significantly reduced in the DC group in comparison with the HC group (P < 0.001). The treatment with EX or UD extract increased the expression of PGC-1α and NRF2 proteins in the heart muscle of animals in the DT and D-UD groups in comparison with the DC group (P < 0.05). Moreover, the expression of these proteins was more pronounced in the DT-UD group. There was not a significant difference between the DT-UD group and the HC group regarding the expression of these proteins (P > 0.05).

CONCLUSIONS

The results of this study showed that treatment with EX and UD extract could treat the disorders which were caused by diabetes in the parameters of cardiac function. Moreover, it was able to improve the expression of the levels of proteins which were involved in mitochondrial biogenesis and its function. Finally, this kind of treatment could attract more attention to the roles of EX and UD extract in the prevention of cardiovascular complications in future studies.

摘要

引言

糖尿病会影响并扰乱线粒体生物合成途径中PGC1α和NRF2蛋白的水平。鉴于荨麻提取物和运动的抗糖尿病特性,本研究旨在探讨荨麻提取物和耐力运动对链脲佐菌素诱导的糖尿病大鼠心脏组织中PGC1α和NRF2蛋白水平的有益影响。

材料与方法

58只雄性Wistar大鼠分为五组(每组n = 12),包括:健康对照组(HC)、糖尿病对照组(DC)、糖尿病荨麻组(D-UD)、糖尿病运动训练组(DT)和糖尿病运动训练荨麻组(DT-UD)。通过腹腔注射链脲佐菌素(45 mg/kg)诱导糖尿病。糖尿病诱导两周后,刺激大鼠进行运动(中等强度/每周5天),并对大鼠灌胃荨麻提取物(50 mg/kg/天),持续六周。在本研究中,采用蛋白质免疫印迹法测量PGC1α和NRF2蛋白的水平。此外,使用心动描记法评估心脏的功能参数(射血分数和缩短分数)。最后,采用生物发光法和酶联免疫吸附测定法测定三磷酸腺苷和柠檬酸合酶的含量。

结果

与其他研究组相比,DC组小鼠的心脏功能参数、线粒体ATP和CS含量受损,并呈下降趋势(P < 0.001)。运动+荨麻提取物治疗能够将这些紊乱的发生率降至最低,并起到线粒体功能保护剂的作用。不同组之间NRF2(F = 17.7,P = 0.001)和PGC-1α(F = 43.7,P = 0.001)线粒体蛋白的表达水平存在显著差异。与HC组相比,DC组中这些蛋白的水平显著降低(P < 0.001)。与DC组相比,运动或荨麻提取物治疗可增加DT组和D-UD组动物心肌中PGC-1α和NRF2蛋白的表达(P < 0.05)。此外,这些蛋白在DT-UD组中的表达更为明显。DT-UD组与HC组在这些蛋白的表达方面无显著差异(P > 0.05)。

结论

本研究结果表明,运动和荨麻提取物治疗可以治疗糖尿病引起的心脏功能参数紊乱。此外,它能够改善参与线粒体生物合成及其功能的蛋白水平的表达。最后,这种治疗方法在未来的研究中可能会使人们更加关注运动和荨麻提取物在预防心血管并发症方面的作用。

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