Division of Endocrinology and Metabolism, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan.
Department of Nursing, Meiho University, Pingtung, Taiwan.
J Appl Physiol (1985). 2019 Aug 1;127(2):356-364. doi: 10.1152/japplphysiol.00184.2019. Epub 2019 May 16.
We previously reported that deep sea water (DSW) prolongs the life span of streptozotocin (STZ)-induced diabetic rats by the compensatory augmentation of the insulin like growth factor (IGF)-I survival signaling and inhibition of apoptosis. Here, we investigated the effects of DSW on cardiac hypertrophy in diabetic rats. Cardiac hypertrophy was induced in rats by using STZ (65 mg/kg) administered via IP injection. DSW was prepared by mixing DSW mineral extracts and desalinated water. Different dosages of DSW-1X (equivalent to 37 mg Mg·kg·day), 2X (equivalent to 74 mg Mg·kg·day) and 3X (equivalent to 111 mg Mg·kg·day) were administered to the rats through gavage for 4 wk. Cardiac hypertrophy was evaluated by the heart weight-to-body weight ratio and the cardiac tissue cross-sectional area after hematoxylin and eosin staining. The protein levels of the cardiac hypertrophy signaling molecules were determined by Western blot. Our results showed that the suppressive effects of the DSW treatment on STZ-induced cardiac hypertrophy were comparable to those of MgSO administration and that the hypertrophic marker brain natriuretic peptide (BNP) was decreased by DSW. In addition, DSW attenuated both the eccentric hypertrophy signaling pathway, IL-6-MEK-STAT3, and the concentric signaling pathway, IGF-II-PKCα-CaMKII, in DM rat hearts. The cardiac hypertrophy-associated activation of extracellular signal-regulated kinase (ERK) and the upregulation of the transcription factor GATA binding protein 4 (GATA4) were also negated by treatment with DSW. The results from this study suggest that DSW could be a potential therapeutic agent for the prevention and treatment of diabetic cardiac hypertrophy. Deep sea water, containing high levels of minerals, improve cardiac hypertrophy in diabetic rats through attenuating the eccentric signaling pathway, IL-6-MEK5-STAT3, and concentric signaling pathway, IGF2-PKCα-CaMKII. The results from this study suggest that deep sea water could be a potential therapeutic agent for the prevention and treatment of diabetic cardiac hypertrophy.
我们之前曾报道过，深海水（DSW）通过补偿性增加胰岛素样生长因子（IGF）-I 存活信号和抑制细胞凋亡来延长链脲佐菌素（STZ）诱导的糖尿病大鼠的寿命。在这里，我们研究了 DSW 对糖尿病大鼠心脏肥大的影响。通过腹腔注射 STZ（65mg/kg）诱导大鼠心脏肥大。DSW 通过混合 DSW 矿物质提取物和去离子水制备。通过灌胃给予大鼠不同剂量的 DSW-1X（相当于 37mgMg·kg·day）、2X（相当于 74mgMg·kg·day）和 3X（相当于 111mgMg·kg·day），持续 4 周。通过心脏重量与体重比和苏木精-伊红染色后的心脏组织横截面面积评估心脏肥大。通过 Western blot 测定心脏肥大信号分子的蛋白水平。结果表明，DSW 处理对 STZ 诱导的心脏肥大的抑制作用与硫酸镁相似，并且 DSW 降低了肥大标志物脑钠肽（BNP）。此外，DSW 减弱了 DM 大鼠心脏中的偏心肥大信号通路，IL-6-MEK-STAT3，和同心信号通路，IGF-II-PKCα-CaMKII。DSW 还否定了心脏肥大相关的细胞外信号调节激酶（ERK）的激活和转录因子 GATA 结合蛋白 4（GATA4）的上调。该研究结果表明，DSW 可能是预防和治疗糖尿病性心脏肥大的潜在治疗剂。富含矿物质的深海水通过减轻偏心信号通路，IL-6-MEK5-STAT3 和同心信号通路，IGF2-PKCα-CaMKII，改善糖尿病大鼠的心脏肥大。该研究结果表明，深海水可能是预防和治疗糖尿病性心脏肥大的潜在治疗剂。
