Lin Yi-Yuan, Hong Yi, Yu Shao-Hong, Wu Xu-Bo, Shyu Woei-Cherng, Chen Jwo-Sheng, Ting Hua, 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). 2019 Jun 1;126(6):1661-1672. doi: 10.1152/japplphysiol.00038.2019. Epub 2019 Apr 18.
This study was to investigate the effects of exercise training on antiapoptotic pathways and mitochondrial biogenesis in ovariectomized hypertensive rats. Histopathological analysis, TUNEL assay, and Western blotting were performed on the excised hearts from female spontaneously hypertensive rats (SHR), which were divided into a sham-operated sedentary hypertensive (SHR-S), a sedentary hypertensive ovariectomized (SHR-O), and hypertensive ovariectomized rats that underwent treadmill exercise training (SHR-OT; 60 min/day, 5 days/wk) for 8 wk, along with normotensive Wistar Kyoto rats (WKY). When compared with the WKY group, the SHR-S group exhibited decreased protein levels of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial OPA-1 (mitochondrial biogenesis) and decreased further in the SHR-O group. The protein levels of p-PI3K, p-Akt, Bcl-2, Bcl-xL (prosurvival pathways), and the protein levels of PGC-1α and mitochondrial OPA1 (mitochondrial biogenesis) were increased in the SHR-OT group, but estrogen receptor (ER)α and ERβ were not changed when compared with the SHR-O group. The protein levels of t-Bid, Bad, Bax, cytosolic cytochrome , activated caspase 9, and activated caspase 3 (mitochondria-dependent apoptotic pathways), as well as Fas ligand, TNF-α, Fas receptors, Fas-associated death domain, activated caspase 8 (Fas receptor-dependent apoptotic pathways) were decreased in the SHR-OT group, when compared with the SHR-O group. Exercise training protection on the coexistence of hypertension and ovariectomy-induced cardiac mitochondria-dependent and Fas receptor-dependent apoptotic pathways by enhancing the Bcl2-related and mitochondrial biogenetic prosurvival pathways might provide a new therapeutic effect on cardiac protection in oophorectomized early postmenopausal hypertensive women. Widely dispersed cardiac apoptosis was found in the coexistence of hypertension and ovariectomy. Exercise training on a treadmill could prevent ovariectomized hypertension-induced widely dispersed cardiac apoptosis via mitochondria-dependent apoptotic pathway (t-Bid, Bad, Bax, cytosolic cytochrome , activated caspase 9, and activated caspase 3) and Fas receptor-dependent apoptotic pathway (Fas ligand, tumor necrosis factor-α, Fas receptors, Fas-associated death domain, activated caspase 8, and activated caspase 3) through enhancing the Bcl2-related (p-PI3K, p-Akt, Bcl-2, Bcl-xL) and mitochondrial biogenetic (PGC-1α and mitochondrial optic atrophy 1) prosurvival pathways.
本研究旨在探讨运动训练对去卵巢高血压大鼠抗凋亡途径和线粒体生物合成的影响。对雌性自发性高血压大鼠（SHR）切除的心脏进行组织病理学分析、TUNEL检测和蛋白质免疫印迹分析，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）以及接受跑步机运动训练（SHR-OT；每天60分钟，每周5天）8周的高血压去卵巢大鼠组，同时设置正常血压的Wistar Kyoto大鼠（WKY）作为对照。与WKY组相比，SHR-S组过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）和线粒体OPA-1（线粒体生物合成）的蛋白水平降低，而SHR-O组进一步降低。SHR-OT组中p-PI3K、p-Akt、Bcl-2、Bcl-xL（促生存途径）的蛋白水平以及PGC-1α和线粒体OPA1（线粒体生物合成）的蛋白水平升高，但与SHR-O组相比，雌激素受体（ER）α和ERβ未发生变化。与SHR-O组相比，SHR-OT组中t-Bid、Bad、Bax、细胞色素c、活化的半胱天冬酶9和活化的半胱天冬酶3（线粒体依赖性凋亡途径）以及Fas配体、肿瘤坏死因子-α、Fas受体、Fas相关死亡结构域、活化的半胱天冬酶8（Fas受体依赖性凋亡途径）的蛋白水平降低。运动训练通过增强Bcl2相关和线粒体生物发生促生存途径，对高血压与去卵巢并存所致的心脏线粒体依赖性和Fas受体依赖性凋亡途径具有保护作用，这可能为绝经后早期去卵巢高血压女性的心脏保护提供一种新的治疗效果。在高血压与去卵巢并存的情况下发现广泛的心脏细胞凋亡。跑步机运动训练可通过增强Bcl2相关（p-PI3K、p-Akt、Bcl-2、Bcl-xL）和线粒体生物发生（PGC-1α和线粒体视神经萎缩蛋白1）促生存途径，预防去卵巢高血压诱导的广泛心脏细胞凋亡，其涉及线粒体依赖性凋亡途径（t-Bid、Bad、Bax、细胞色素c、活化的半胱天冬酶9和活化的半胱天冬酶3）和Fas受体依赖性凋亡途径（Fas配体、肿瘤坏死因子-α、Fas受体、Fas相关死亡结构域、活化的半胱天冬酶8和活化的半胱天冬酶3）。
