肾素-血管紧张素系统阻断可改善 2 型糖尿病大鼠模型心脏心律失常和交感神经重构。

Blockade of Renin Angiotensin System Ameliorates the Cardiac Arrhythmias and Sympathetic Neural Remodeling in Hearts of Type 2 DM Rat Model.

机构信息

Medical Physiology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

Department of internal Medicine and endocrinology, Delta University, Gamasa, Egypt.

出版信息

Endocr Metab Immune Disord Drug Targets. 2020;20(3):464-478. doi: 10.2174/1871530319666190809150921.

DOI:10.2174/1871530319666190809150921

PMID:31544705

Abstract

OBJECTIVE

The present study was designed to investigate the effects of renin angiotensin system (RAS) blockade on cardiac arrhythmias and sympathetic nerve remodelling in heart tissues of type 2 diabetic rats.

METHODS

Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group: normal rats, b) DM group; after type 2 diabetes induction, rats received 2ml oral saline daily for 4 weeks, c) DM+ ACEi: after type 2 diabetes induction, rats were treated with enalapril (10 mg/kg, orally for 4 weeks) and d) DM+ ARBs: after type 2 diabetes induction, rats were treated with losartan (30 mg/kg, orally for 4 weeks).

RESULTS

In type 2 diabetic rats, the results demonstrated significant prolongation in Q-T interval and elevation of blood sugar, HOMA-IR index, TC, TGs, LDL, serum CK-MB, myocardial damage, myocardial MDA, myocardial norepinephrine and tyrosine hydroxylase (TH) density with significant reduction in serum HDL, serum insulin and myocardial GSH and CAT. On the other hand, blockade of RAS at the level of either ACE by enalapril or angiotensin (Ag) receptors by losartan resulted in significant improvement in ECG parameters (Q-T), cardiac enzymes (CK-MB), cardiac morphology, myocardial oxidative stress (low MDA, high CAT and GSH) and myocardial TH density.

CONCLUSION

RAS plays a role in the cardiac sympathetic nerve sprouting and cardiac arrhythmias induced by type 2 DM and its blockade might have a cardioprotective effect via attenuation of sympathetic nerve fibres remodelling, myocardial norepinephrine contents and oxidative stress.

摘要

目的

本研究旨在探讨肾素血管紧张素系统（RAS）阻断对 2 型糖尿病大鼠心脏组织心律失常和交感神经重塑的影响。

方法

32 只雄性 Sprague Dawley 大鼠随机分为 4 组：a）正常对照组：正常大鼠；b）DM 组：2 型糖尿病诱导后，每日给予 2ml 口服生理盐水 4 周；c）DM+ACEi：2 型糖尿病诱导后，给予依那普利（10mg/kg，口服 4 周）治疗；d）DM+ARBs：2 型糖尿病诱导后，给予氯沙坦（30mg/kg，口服 4 周）治疗。

结果

在 2 型糖尿病大鼠中，结果表明 Q-T 间期显著延长，血糖、HOMA-IR 指数、TC、TGs、LDL、血清 CK-MB、心肌损伤、心肌 MDA、心肌去甲肾上腺素和酪氨酸羟化酶（TH）密度升高，而血清 HDL、血清胰岛素和心肌 GSH、CAT 降低。另一方面，通过依那普利阻断 ACE 水平或通过氯沙坦阻断血管紧张素（Ag）受体阻断 RAS，可显著改善心电图参数（Q-T）、心肌酶（CK-MB）、心脏形态、心肌氧化应激（低 MDA、高 CAT 和 GSH）和心肌 TH 密度。