二eckol通过调节自发性高血压大鼠中的血管紧张素II 1型受体和NADPH氧化酶来减轻肌肉萎缩。
Dieckol Reduces Muscle Atrophy by Modulating Angiotensin Type II Type 1 Receptor and NADPH Oxidase in Spontaneously Hypertensive Rats.
作者信息
Oh Seyeon, Yang Jin Young, Park Chul Hyun, Son Kuk Hui, Byun Kyunghee
机构信息
Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon 21999, Korea.
Department of Thoracic and Cardiovascular Surgery, Gil Medical Center, Gachon University, Incheon 21565, Korea.
出版信息
Antioxidants (Basel). 2021 Sep 30;10(10):1561. doi: 10.3390/antiox10101561.
The renin-angiotensin system is involved in the development of hypertension and sarcopenia. Increased levels of angiotensin II (Ang II) lead to upregulation of Ang II type 1 receptor (AT1R), which results in increasing reactive oxygen species (ROS) by NAD(P)H oxidase (Nox). Increased ROS led to increased helper T17 (Th17) and decreased regulatory T (Treg) cells through HIF-1α. Increased Th17 secretes more IL-17, leading to increased NF-κB and muscle atrophy. We evaluated the effect of extracts (ECE) and dieckol (DK) on attenuating muscle atrophy by decreasing AT1R and NOX activity in spontaneous hypertensive rats (SHRs). The serum levels of Ang II and expression of AT1R in the muscle were higher in SHRs than in normotensive animals of Wistar-Kyoto rats (2.4 and 1.8 times higher than WKY, respectively). The expression of AT1R decreased by ECE or DK (0.62 and 0.84 times lower than SHR, respectively). In SHRs, the expression of Nox 1, 2, and 4 were increased (1.2-1.15 times higher than WKY) but were decreased by the administration of ECE (0.8-0.9 times lower than SHR) or DK (0.7-0.9 times lower than SHR). The Nox activity was increased in SHRs (2.3 times more than WKY) and it was decreased by ECE (0.9 times lower than SHRs) and DK (0.9 times lower than SHRs). The expression of HIF-1α, a marker of Th17 (RORγt), and cytokine secreted by Th17 (IL-17) was increased in SHRs and was decreased by ECE or DK. The marker of Treg (Foxp3) and cytokine secreted from Treg cells (IL-10) was decreased in SHRs and was increased by ECE or DK. The expression of NF-κB/IL-1β/TNF-α and MuRF-1/MAFbx/atrogin-1 was increased in SHRs and these were decreased by ECE or DK. The cross-sectional area of muscle fiber was decreased in SHRs (0.7 times lower than WKY) and was increased by ECE (1.3 times greater than SHR) or DK (1.5 times greater than SHR). In conclusion, ECE or DK leads to a decreased expression of AT1R and Nox activity which modulates Th17/Treg balance and consequently, decreased muscle atrophy.
肾素-血管紧张素系统参与高血压和肌肉减少症的发展。血管紧张素II（Ang II）水平升高导致血管紧张素II 1型受体（AT1R）上调，这会通过NAD(P)H氧化酶（Nox）增加活性氧（ROS）。ROS增加通过缺氧诱导因子-1α（HIF-1α）导致辅助性T17细胞（Th17）增加和调节性T细胞（Treg）减少。增加的Th17分泌更多白细胞介素-17（IL-17），导致核因子κB（NF-κB）增加和肌肉萎缩。我们评估了提取物（ECE）和二萘嵌苯（DK）通过降低自发性高血压大鼠（SHR）的AT1R和Nox活性来减轻肌肉萎缩的作用。SHR血清中Ang II水平和肌肉中AT1R的表达高于正常血压的Wistar-Kyoto大鼠（分别比WKY高2.4倍和1.8倍）。ECE或DK可使AT1R表达降低（分别比SHR低0.62倍和0.84倍）。在SHR中，Nox 1、2和4的表达增加（比WKY高1.2 - 1.15倍），但给予ECE（比SHR低0.8 - 0.9倍）或DK（比SHR低0.7 - 0.9倍）后表达降低。SHR中Nox活性增加（比WKY高2.3倍），而ECE（比SHR低0.9倍）和DK（比SHR低0.9倍）可使其降低。SHR中Th17的标志物HIF-1α、维甲酸相关孤儿受体γt（RORγt）以及Th17分泌的细胞因子（IL-17）表达增加，而ECE或DK可使其降低。Treg的标志物叉头框蛋白3（Foxp3）和Treg细胞分泌的细胞因子（IL-10）在SHR中降低，而ECE或DK可使其增加。SHR中NF-κB/白细胞介素-1β/肿瘤坏死因子-α以及肌肉萎缩相关基因1（MuRF-1）/肌肉萎缩相关因子（MAFbx）/萎缩基因1（atrogin-1）的表达增加，而ECE或DK可使其降低。SHR中肌纤维横截面积减小（比WKY低0.7倍），而ECE（比SHR大1.3倍）或DK（比SHR大1.5倍）可使其增加。总之，ECE或DK导致AT1R表达降低和Nox活性降低，从而调节Th17/Treg平衡，进而减少肌肉萎缩。
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