Chen Gangbin, Yang Li, Zhong Lintao, Kutty Shelby, Wang Yuegang, Cui Kai, Xiu Jiancheng, Cao Shiping, Huang Qiaobing, Liao Wangjun, Liao Yulin, Wu Juefei, Zhang Wenzhu, Bin Jianping
State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, P.R. China.
Sci Rep. 2016 Jul 29;6:30643. doi: 10.1038/srep30643.
Hydrogen sulfide (H2S) is an attractive agent for myocardial ischemia-reperfusion injury, however, systemic delivery of H2S may cause unwanted side effects. Ultrasound targeted microbubble destruction has become a promising tool for organ specific delivery of bioactive substance. We hypothesized that delivery of H2S by ultrasound targeted microbubble destruction attenuates myocardial ischemia-reperfusion injury and could avoid unwanted side effects. We prepared microbubbles carrying hydrogen sulfide (hs-MB) with different H2S/C3F8 ratios (4/0, 3/1, 2/2, 1/3, 0/4) and determined the optimal ratio. Release of H2S triggered by ultrasound was investigated. The cardioprotective effect of ultrasound targeted hs-MB destruction was investigated in a rodent model of myocardial ischemia-reperfusion injury. The H2S/C3F8 ratio of 2/2 was found to be an optimal ratio to prepare stable hs-MB with higher H2S loading capability. Ultrasound targeted hs-MB destruction triggered H2S release and increased the concentration of H2S in the myocardium and lung. Ultrasound targeted hs-MB destruction limited myocardial infarct size, preserved left ventricular function and had no influence on haemodynamics and respiratory. This cardioprotective effect was associated with alleviation of apoptosis and oxidative stress. Delivery of H2S to the myocardium by ultrasound targeted hs-MB destruction attenuates myocardial ischemia-reperfusion injury and may avoid unwanted side effects.
硫化氢（H2S）是一种用于心肌缺血再灌注损伤的有吸引力的药物，然而，全身性给予H2S可能会引起不良副作用。超声靶向微泡破坏已成为一种用于生物活性物质器官特异性递送的有前景的工具。我们假设通过超声靶向微泡破坏递送H2S可减轻心肌缺血再灌注损伤，并可避免不良副作用。我们制备了具有不同H2S/C3F8比例（4/0、3/1、2/2、1/3、0/4）的携带硫化氢的微泡（hs-MB），并确定了最佳比例。研究了超声触发的H2S释放。在心肌缺血再灌注损伤的啮齿动物模型中研究了超声靶向hs-MB破坏的心脏保护作用。发现2/2的H2S/C3F8比例是制备具有更高H2S负载能力的稳定hs-MB的最佳比例。超声靶向hs-MB破坏触发了H2S释放，并增加了心肌和肺中H2S的浓度。超声靶向hs-MB破坏限制了心肌梗死面积，保留了左心室功能，并且对血流动力学和呼吸没有影响。这种心脏保护作用与细胞凋亡和氧化应激的减轻有关。通过超声靶向hs-MB破坏将H2S递送至心肌可减轻心肌缺血再灌注损伤，并可能避免不良副作用。
