Lin Yi-Yuan, Hong Yi, Zhou Ming-Cheng, Huang Hai-Liang, Shyu Woei-Cherng, Chen Jwo-Sheng, Ting Hua, Cheng Yu-Jung, Yang Ai-Lun, Lee Shin-Da
School of Rehabilitation Medicine, Weifang Medical University, Shandong, China.
Department of Physical Therapy, Asia University, Taichung, Taiwan.
J Appl Physiol (1985). 2020 Apr 1;128(4):1033-1043. doi: 10.1152/japplphysiol.00844.2019. Epub 2020 Mar 12.
This study investigated the effects of exercise training on cardiac inflammatory and cardiac fibrotic pathways in female spontaneously hypertensive rats (SHR), which were divided into a sham-operated sedentary hypertensive group (SHR-S), a sedentary hypertensive ovariectomized group (SHR-O), or a hypertensive ovariectomized group with treadmill exercise training (SHR-OT; 60 min/day, 5 days/wk) for 8 wk. Normotensive female Wistar-Kyoto rats (WKY) served as controls. SOD and catalase (CAT) activities were significantly increased in the SHR-OT group, when compared with the SHR-S or SHR-O groups. The protein levels of estrogen receptor (ER)-α and ER-β became decreased in the SHR-O group, when compared with the WKY or SHR-S groups, but were not changed in the SHR-OT group. The protein level of the angiotensin II type I receptor (ATR) was increased in the SHR-S group but did not further change in the SHR-O group, whereas it was decreased in the SHR-OT group. The inflammatory-related protein levels of TNF-α, p-NF-κB, cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), and IL-6, as well as the fibrotic-related protein levels of transforming growth factor-β (TGF-β), p-Smad2/3, connective tissue growth factor (CTGF), tissue-type plasminogen activator (tPA), matrix metalloproteinase (MMP)-9, and collagen I were increased in the SHR-S group and increased further in the SHR-O group, whereas they were decreased in the SHR-OT group. The coexistence of hypertension and ovariectomy additively increased cardiac inflammatory and fibrotic pathways partially through hypertension-enhanced ATR and ovariectomy-depressed estrogen receptors. Exercise training appeared to suppress hypertensive ovariectomized heart-induced inflammatory and fibrotic pathways possibly through decreasing ATR but not through estrogen receptors. The coexistence of hypertension and ovariectomy appeared to increase cardiac inflammatory and fibrotic pathways likely through hypertension-enhanced angiotensin II type I receptor and ovariectomy-depressed estrogen receptors. Exercise training on a treadmill could prevent hypertensive ovariectomized heart-induced cardiac inflammation and fibrosis via an inflammatory pathway [TNF-α, p-IKK-α/β, p-NF-κB, cyclooxygenase 2 (COX-2), iNOS, and IL-6] and fibrotic pathway [transforming growth factor-β (TGF-β), p-Smad2/3, connective tissue growth factor (CTGF), tissue-type plasminogen activator (tPA), matrix metalloproteinase (MMP)-9, and collagen I] possibly through decreasing angiotensin II type I receptor but not through estrogen receptors.
本研究调查了运动训练对雌性自发性高血压大鼠（SHR）心脏炎症和心脏纤维化途径的影响，这些大鼠被分为假手术久坐高血压组（SHR-S）、久坐高血压去卵巢组（SHR-O）或进行跑步机运动训练的高血压去卵巢组（SHR-OT；每天60分钟，每周5天），为期8周。正常血压的雌性Wistar-Kyoto大鼠（WKY）作为对照。与SHR-S组或SHR-O组相比，SHR-OT组的超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性显著增加。与WKY组或SHR-S组相比，SHR-O组雌激素受体（ER）-α和ER-β的蛋白水平降低，但SHR-OT组未发生变化。血管紧张素II 1型受体（ATR）的蛋白水平在SHR-S组中升高，在SHR-O组中未进一步变化，而在SHR-OT组中降低。促炎相关蛋白肿瘤坏死因子-α（TNF-α）、磷酸化核因子-κB（p-NF-κB）、环氧化酶2（COX-2）、诱导型一氧化氮合酶（iNOS）和白细胞介素-6（IL-6），以及纤维化相关蛋白转化生长因子-β（TGF-β）、磷酸化Smad2/3、结缔组织生长因子（CTGF）、组织型纤溶酶原激活剂（tPA）、基质金属蛋白酶（MMP）-9和I型胶原在SHR-S组中升高，在SHR-O组中进一步升高，而在SHR-OT组中降低。高血压和去卵巢的共同存在通过高血压增强的ATR和去卵巢降低的雌激素受体部分地累加增加了心脏炎症和纤维化途径。运动训练似乎通过降低ATR而不是通过雌激素受体抑制高血压去卵巢心脏诱导的炎症和纤维化途径。高血压和去卵巢的共同存在似乎通过高血压增强的血管紧张素II 1型受体和去卵巢降低的雌激素受体增加了心脏炎症和纤维化途径。跑步机运动训练可以通过炎症途径 [TNF-α、磷酸化IκB激酶α/β（p-IKK-α/β）、p-NF-κB、COX-2、iNOS和IL-6] 和纤维化途径 [TGF-β、p-Smad2/3、CTGF、tPA、MMP-9和I型胶原]预防高血压去卵巢心脏诱导的心脏炎症和纤维化，可能是通过降低血管紧张素II 1型受体而不是通过雌激素受体。
