Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Organ Transplantation, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Organ Transplantation, Ministry of Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Ultrasonography, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Hubei Provincial Key Laboratory of Molecular Imaging, Wuhan, China.
Life Sci. 2019 Jul 1;228:35-46. doi: 10.1016/j.lfs.2019.04.057. Epub 2019 Apr 24.
The shortage of donor hearts could be alleviated with the use of the allografts from donation after circulatory death (DCD). Here, we evaluated the protective effect of melatonin on myocardial ischemia/reperfusion (MI/R) injury in a DCD heart model after ex vivo perfusion.
Donor hearts were harvested from DCD model rats pre-treated with or without melatonin and subjected to 30 min of ex vivo perfusion, followed by transplantation. Tissue samples were obtained at 3, 12, and 24 h after heart transplantation. Myocardial oedema was evaluated based on the water content and wet/dry ratio, while inflammation was examined with hematoxylin & eosin staining. The expression levels of matrix metalloproteinase-9, interleukin-6, and tumour necrosis factor-α were evaluated. Oxidative stress level was determined from the content of malondialdehyde, activities of superoxide dismutase and glutathione peroxidase, and expression of Nrf2, NQO1 and cytochrome-C. Myocardial apoptosis was detected with TUNEL assay and measurement of the expression levels of Bax, Bcl-2, caspase-3, and cleaved caspase-3. The activation of the JAK2/STAT3 signalling pathway was evaluated by determining the levels of p-JAK2 and p-STAT3.
Melatonin pre-treatment protected the heart from MI/R by reducing myocardial oedema and inflammation, attenuating oxidative stress, and decreasing myocardial apoptosis. Furthermore, the JAK2/STAT3 signalling pathway was activated after melatonin treatment during MI/R. The protective effects of melatonin were abolished by AG490.
Melatonin pre-treatment protected the heart from MI/R in a DCD heart model after ex vivo perfusion. Melatonin exerted cardioprotective effects through the activation of the JAK2/STAT3 signalling pathway.
使用来自循环死亡后捐献（DCD）的同种异体移植物可以缓解供心短缺的问题。在这里，我们评估了褪黑素对离体灌流后 DCD 心脏模型心肌缺血/再灌注（MI/R）损伤的保护作用。
从预先用褪黑素预处理或未用褪黑素预处理的 DCD 模型大鼠中获取供体心脏，并进行 30 分钟的离体灌注，然后进行移植。在心脏移植后 3、12 和 24 小时获取组织样本。根据水含量和湿/干比评估心肌水肿，通过苏木精和伊红染色检查炎症。评估基质金属蛋白酶-9、白细胞介素-6 和肿瘤坏死因子-α的表达水平。通过测定丙二醛含量、超氧化物歧化酶和谷胱甘肽过氧化物酶的活性以及 Nrf2、NQO1 和细胞色素-C 的表达来确定氧化应激水平。通过 TUNEL 检测和 Bax、Bcl-2、caspase-3 和 cleaved caspase-3 的表达水平检测心肌细胞凋亡。通过测定 p-JAK2 和 p-STAT3 的水平来评估 JAK2/STAT3 信号通路的激活情况。
褪黑素预处理通过减少心肌水肿和炎症、减轻氧化应激和减少心肌细胞凋亡来保护心脏免受 MI/R。此外，在 MI/R 期间，褪黑素处理后激活了 JAK2/STAT3 信号通路。AG490 消除了褪黑素的保护作用。
褪黑素预处理通过激活 JAK2/STAT3 信号通路，在离体灌流后的 DCD 心脏模型中保护心脏免受 MI/R。
