Effects of combined treatment with blood flow restriction and low-current electrical stimulation on capillary regression in the soleus muscle of diabetic rats

Effects of combined treatment with blood flow restriction and low-current electrical stimulation on capillary regression in the soleus muscle of diabetic rats
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血流限制与小电流电刺激联合治疗对糖尿病大鼠比目鱼肌毛细血管退化的影响

DOI:
10.1152/japplphysiol.00366.2021
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发表时间:
2021
期刊:
影响因子:
3.3
通讯作者:
Fujino H
Fujino H
中科院分区:
医学2区
文献类型:
--
作者:
Tanaka M;Morifuji T;Sugimoto K;Akasaka H;Fujimoto T;Yoshikawa M;Nakanishi R;Kondo H;Fujino H

文献摘要

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为了阐明血流限制(Bfr)下的低电流电刺激(ES)对糖尿病相关的骨骼肌毛细血管退化的预防作用,我们评估了三维毛细血管结构和血管生成因子的变化。将24只Goto-Kakizaki大鼠随机分为4组:糖尿病(DM)组、Bfr(DM + Bfr)组、电刺激(DM + ES)组和Bfr + ES(DM + Bfr + ES)组。6只健康Wistar大鼠作为年龄匹配的对照。在大鼠大腿周围使用压力袖带(80 mmHg)进行Bfr,并将低电流ES应用于大鼠的小腿肌肉。电流强度设定为最大等长收缩的30%(24-30 mA)。每周给药3次,共8 wk。糖尿病组比目鱼肌毛细血管直径和体积减少,抗血管生成因子水平升高。此外,DM引起缺氧诱导因子的增加。单独地,Bfr或ES治疗未能抑制DM相关的毛细血管消退和抗血管生成因子的增加。然而,Bfr和ES联合治疗通过抑制增加的抗血管生成因子和增强白细胞介素-15表达、线粒体生物发生因子和促血管生成因子来预防DM相关的毛细血管消退。因此,DM相关的毛细血管退化抑制的联合治疗可能会阻止增加的抗血管生成因子的影响,并提高proangiogenicfactor.NEW &值得注意的是,血流限制和低强度电刺激的联合治疗减弱了2型糖尿病(T2 D)相关的毛细血管退化的骨骼肌。该治疗通过抑制肌内慢性缺氧来抑制T2 D相关的抗血管生成因子的增加;它可以通过增强促血管生成因子来抑制肌内慢性缺氧。这些结果表明,联合治疗可能是预防骨骼肌中T2 D相关毛细血管消退的有效治疗干预。
To clarify the preventive effects of low-current electrical stimulation (ES) under blood flow restriction (Bfr) on diabetes-associated capillary regression in skeletal muscles, we assessed the changes in three-dimensional capillary architecture and angiogenic factors. Twenty-four Goto–Kakizaki rats were randomly divided into four groups: the sedentary diabetes mellitus (DM), Bfr (DM + Bfr), electrical stimulation (DM + ES), and Bfr plus ES (DM + Bfr + ES) groups. Six healthy Wistar rats were used as age-matched controls. Bfr was performed using pressure cuffs (80 mmHg) around the thighs of the rats, and low-current ES was applied to the calf muscles of the rats. The current intensity was set at 30% of the maximal isometric contraction (24–30 mA). The treatments were delivered three times a week for 8 wk. In the DM group, the capillary diameter and volume of the soleus muscle decreased, and, the antiangiogenic factor level increased. Furthermore, DM caused an increase in the hypoxia-inducible factor. Individually, Bfr or ES treatments failed to inhibit the DM-associated capillary regression and increase in antiangiogenic factor. However, combined treatment with Bfr and ES prevented DM-associated capillary regression via inhibition of the increased antiangiogenic factor and enhancement of interleukin-15 expression, mitochondrial biogenesis factors, and a proangiogenic factor. Therefore, DM-associated capillary regression inhibited by the combined treatment may prevent the effects of the increased antiangiogenic factor and enhance the proangiogenic factor.NEW & NOTEWORTHYThe combined treatment of blood flow restriction and low intensity electrical stimulation attenuated type 2 diabetes (T2D)-associated capillary regression in the skeletal muscles. The treatment inhibits the T2D-associated increase in antiangiogenic factors via inhibition of intramuscular chronic hypoxia; it can inhibit intramuscular chronic hypoxia by enhancing proangiogenic factors. These results suggest that the combined treatment may be an effective therapeutic intervention for the prevention of T2D-associated capillary regression in the skeletal muscles.