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肥胖小鼠的血管周围脂肪组织和微血管内皮功能障碍:脂联素受体(AdipoR1)和 peNOS 对有氧运动的有益作用。

Perivascular adipose tissue and microvascular endothelial dysfunction in obese mice: Beneficial effects of aerobic exercise in adiponectin receptor (AdipoR1) and peNOS.

机构信息

Laboratory of Vascular Biology, Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil.

出版信息

Clin Exp Pharmacol Physiol. 2021 Oct;48(10):1430-1440. doi: 10.1111/1440-1681.13550. Epub 2021 Jul 21.

DOI:10.1111/1440-1681.13550
PMID:34260769
Abstract

In the present study, we aim to investigate the effects of aerobic physical training on perivascular adipose tissue (PVAT)-induced microvascular dysfunction of the femoral artery in obese mice. Microvascular reactivity was evaluated in control sedentary (c-SD), obese sedentary (o-SD) and obese trained (o-TR) male mice (C57BL6/JUnib), in the absence (PVAT-) or the presence (PVAT+) of femoral artery PVAT. We also analyzed protein expression, vascular nitric oxide (NO) production and reactive oxygen species (ROS) generation in PVAT. The blood glucose, triglycerides and total cholesterol levels were increased in the o-SD group, when compared with the c-SD group. The maximal responses and the potency to acetylcholine (ACh) were decreased in PVAT+ compared with PVAT- rings in the o-SD group, accompanied by a decrease in vascular protein expression of peNOS , Cu/Zn-SOD, leptin receptor (Ob-R) and adiponectin receptor (AdipoR1). The protein expression of leptin increased and that of adiponectin decreased in PVAT. Additionally, vascular NO production was reduced and ROS generation was enhanced in PVAT in the o-SD group. Aerobic exercise training was effective for normalizing ACh relaxation response, vascular NO production and ROS generation in the o-TR group. It partially re-established the vascular protein expression of peNOS and the PVAT leptin; normalized the vascular Cu/Zn-SOD and AdipoR1 protein expressions. In obese sedentary mice, the presence of PVAT is involved in the process of microvascular dysfunction of the femoral artery in a pathway associated with increased inflammation and ROS generation. The aerobic exercise training normalized the vascular response, the NO production and/or bioavailability and oxidative stress, with improved vascular expressions of Cu/Zn-SOD, peNOS , and AdipoR1.

摘要

在本研究中,我们旨在研究有氧体能训练对肥胖小鼠血管周围脂肪组织(PVAT)诱导的股动脉微血管功能障碍的影响。在不存在(PVAT-)或存在(PVAT+)股动脉 PVAT 的情况下,评估了对照久坐(c-SD)、肥胖久坐(o-SD)和肥胖训练(o-TR)雄性小鼠(C57BL6/JUnib)的微血管反应性。我们还分析了 PVAT 中的蛋白表达、血管一氧化氮(NO)产生和活性氧(ROS)生成。与 c-SD 组相比,o-SD 组的血糖、甘油三酯和总胆固醇水平升高。与 o-SD 组的 PVAT-环相比,PVAT+环中乙酰胆碱(ACh)的最大反应和效力降低,同时血管蛋白表达 peNOS、Cu/Zn-SOD、瘦素受体(Ob-R)和脂联素受体(AdipoR1)减少。PVAT 中的瘦素蛋白表达增加,脂联素蛋白表达减少。此外,o-SD 组中血管 NO 生成减少,ROS 生成增加。有氧运动训练可使 o-TR 组的 ACh 松弛反应、血管 NO 生成和 ROS 生成正常化。它部分恢复了 peNOS 和 PVAT 瘦素的血管蛋白表达;使血管 Cu/Zn-SOD 和 AdipoR1 蛋白表达正常化。在肥胖久坐的小鼠中,PVAT 的存在涉及与炎症和 ROS 生成增加相关的股动脉微血管功能障碍的过程。有氧运动训练使血管反应、NO 生成和/或生物利用度以及氧化应激正常化,改善了 Cu/Zn-SOD、peNOS 和 AdipoR1 的血管表达。

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