Department of Surgery, University of Colorado Denver Health Sciences Center, Aurora, Colorado 80045, USA.
J Surg Res. 2011 Dec;171(2):379-85. doi: 10.1016/j.jss.2011.04.009. Epub 2011 May 4.
Thyroid hormone can have positive effects on the cardiovascular system but its therapeutic potential is limited secondary to its adverse effects. DITPA (3,5-diiodothyroproprionic acid) is a synthetic thyroid hormone analog with positive inotropic effects similar to thyroid hormone but with minimal systemic effects. DITPA has previously been shown to reduce pathologic remodeling and improve cardiac output following myocardial infarction; however, few studies have examined the role of DITPA in determining infarct size or the early inflammatory response following myocardial ischemia. We examined the role of DITPA in the acute phase following infarction.
Mice were subjected to surgical induction of myocardial infarction and were then randomized to receive daily injections of DITPA or vehicle control. After 3 d, animals were sacrificed and infarct size was determined by H and E staining. Myocardial macrophage and neutrophil accumulation was determined by immunofluorescent staining. Immunoblotting and enzyme-linked immunosorbent assay (ELISA) were used to examine the levels of intercellular adhesion molecule-1 (ICAM-1), keratinocyte-derived chemokine (KC), monocyte chemoattractant protein (MCP-1), and interleukin 6 (IL-6) in homogenates from the ischemic tissue.
Compared with vehicle control, DITPA treated animals had smaller infarcts (52.1%±5.7% versus 37.3%±3.6%, P<0.05) and decreased macrophage (32±4 versus 14±1 cells/HPF, P<0.05, and neutrophil (14±2 versus 7±1 cells/HPF, P<0.05) accumulation. Myocardial ICAM-1, (2.37±0.4 versus 1.1±0.2, P<0.05), KC levels (33.32±12.4 pg/mg, versus 21.24±8.9 pg/mg, P<0.05), and IL-6 levels (112.3±78 pg/mg versus 37.3±25.9 pg/mg, P<0.05) were also reduced in the DITPA treated group, while MCP-1 levels were equivalent between groups.
Treatment with DITPA attenuates the acute inflammatory response and reduces myocardial infarct size. The reduction in myocardial ICAM-1, KC, and IL-6 levels in the DITPA group was associated with a decrease in macrophage and neutrophil accumulation.
甲状腺激素对心血管系统有积极作用，但由于其副作用，其治疗潜力有限。DITPA（3,5-二碘甲状腺原氨酸丙酸）是一种合成的甲状腺激素类似物，具有与甲状腺激素相似的正性肌力作用，但全身作用较小。DITPA 先前已被证明可减少心肌梗死后的病理性重构并改善心输出量；然而，很少有研究检查 DITPA 在确定心肌缺血后梗死面积或早期炎症反应中的作用。我们检查了 DITPA 在梗死急性期的作用。
小鼠接受手术诱导心肌梗死，然后随机接受 DITPA 或载体对照的每日注射。3d 后，处死动物，通过 H 和 E 染色确定梗死面积。通过免疫荧光染色确定心肌巨噬细胞和中性粒细胞的积累。免疫印迹和酶联免疫吸附试验（ELISA）用于检查缺血组织匀浆中细胞间黏附分子-1（ICAM-1）、角质细胞衍生趋化因子（KC）、单核细胞趋化蛋白 1（MCP-1）和白细胞介素 6（IL-6）的水平。
与载体对照组相比，DITPA 治疗组的梗死面积较小（52.1%±5.7%对 37.3%±3.6%，P<0.05），巨噬细胞（32±4 对 14±1 细胞/HPF，P<0.05）和中性粒细胞（14±2 对 7±1 细胞/HPF，P<0.05）积累减少。心肌 ICAM-1（2.37±0.4 对 1.1±0.2，P<0.05）、KC 水平（33.32±12.4pg/mg，对 21.24±8.9pg/mg，P<0.05）和 IL-6 水平（112.3±78pg/mg 对 37.3±25.9pg/mg，P<0.05）在 DITPA 治疗组也降低，而 MCP-1 水平在两组之间相当。
DITPA 治疗可减轻急性炎症反应并减少心肌梗死面积。DITPA 组心肌 ICAM-1、KC 和 IL-6 水平的降低与巨噬细胞和中性粒细胞积累减少有关。
