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通过激活2型糖尿病大鼠中的Mir-126及相关靶蛋白增强心脏血管生成:丁酸钠与自愿运动疗法的联合挽救作用

Cardiac angiogenesis enhances by activating Mir-126 and related target proteins in type 2 diabetic rats: Rescue combination effect of Sodium butyrate and voluntary exercise therapy.

作者信息

Dariushnejad Hassan, Roshanravan Neda, Pirzeh Lale, Cheraghi Mostafa, Ghorbanzadeh Vajihe

机构信息

Department of Medical Biotechnology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.

Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

J Diabetes Metab Disord. 2023 Feb 21;22(1):753-761. doi: 10.1007/s40200-023-01198-1. eCollection 2023 Jun.

Abstract

OBJECTIVE

type 2 diabetes, metabolic disorder, is one of the main risk factors for cardiovascular disease, leading to angiogenesis injury. The present study wanted to discover the effect of sodium butyrate (NaB) and voluntary exercise, alone or together, on miR-126 and related proteins in rats with type 2 diabetes.

METHODS

thirty-five male Wistar rats (200-250 g) were randomly divided into five groups: control, diabetes, diabetes-NaB, diabetes-exercise, and diabetes-NaB-exercise. Type 2 diabetes was induced by intraperitoneal injection of streptozotocin (35 mg/kg) and high-fat diet. The rats were then administrated NaB (200 mg/kg. ip) or were subjected to voluntary exercise, or combined NaB and voluntary exercise for 8 weeks. MiR-126 expression in the cardiac tissue was determined by real-time PCR, and the SPRED-1 and RAF proteins expression levels were measured by western blot.

RESULTS

NaB and voluntary exercise up-regulated cardiac miR-126 and RAF expression levels and down-regulated SPRED-1 in cardiac tissue of type 2 diabetic rats. Moreover, the combination of NaB and voluntary exercise amplified their effects on those parameters. Both NaB and voluntary exercise or together markedly modulated serum glucose and HbA1c.

CONCLUSION

The present findings demonstrated that NaB combined with exercise could improve cardiac angiogenesis by increasing miR-126 and affecting related proteins. Thus, NaB together with voluntary exercise might be a promising intervention for the treatment and prevention of type 2 diabetes.

摘要

目的

2型糖尿病作为一种代谢紊乱疾病,是心血管疾病的主要危险因素之一,可导致血管生成损伤。本研究旨在探究丁酸钠(NaB)和自主运动单独或联合应用对2型糖尿病大鼠miR-126及相关蛋白的影响。

方法

将35只雄性Wistar大鼠(200 - 250 g)随机分为五组:对照组、糖尿病组、糖尿病 - NaB组、糖尿病 - 运动组和糖尿病 - NaB - 运动组。通过腹腔注射链脲佐菌素(35 mg/kg)和高脂饮食诱导2型糖尿病。随后,大鼠接受NaB(200 mg/kg,腹腔注射)或进行自主运动,或联合应用NaB和自主运动,持续8周。采用实时PCR测定心脏组织中miR-126的表达,通过蛋白质印迹法检测SPRED-1和RAF蛋白的表达水平。

结果

NaB和自主运动上调了2型糖尿病大鼠心脏组织中miR-126和RAF的表达水平,并下调了SPRED-1的表达。此外,NaB和自主运动联合应用增强了它们对这些参数的影响。NaB、自主运动单独或联合应用均显著调节了血糖和糖化血红蛋白(HbA1c)水平。

结论

本研究结果表明,NaB联合运动可通过增加miR-126并影响相关蛋白来改善心脏血管生成。因此,NaB与自主运动联合应用可能是治疗和预防2型糖尿病的一种有前景的干预措施。

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