Ethyl pyruvate modulates delayed paralysis following thoracic aortic ischemia reperfusion in mice

被引:6
作者
Bao-Ngoc Nguyen [1 ]
Albadawi, Hassan [1 ]
Oklu, Rahmi [2 ]
Crawford, Robert S. [1 ]
Fink, Mitchell P. [3 ]
Cambria, Richard P. [1 ]
Watkins, Michael T. [1 ]
机构
[1] Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, Dept Radiol, Div Intervent Radiol, Boston, MA USA
[3] Univ Pittsburgh, Sch Med, Dept Crit Care, Pittsburgh, PA USA
基金
美国国家卫生研究院;
关键词
SPINAL-CORD ISCHEMIA; MOUSE MODEL; INJURY; CELLS; ACTIVATION; APOPTOSIS; PERFUSION; NECROSIS; DAMAGE; REPAIR;
D O I
10.1016/j.jvs.2015.06.214
中图分类号
R61 [外科手术学];
学科分类号
摘要
Objective: Delayed paralysis is an unpredictable problem for patients undergoing complex repair of the thoracic/thoracoabdominal aorta. These experiments were designed to determine whether ethyl pyruvate (EP), a potent and-inflammatory and antioxidant agent, might ameliorate delayed paralysis following thoracic aortic ischemia reperfusion (TAR). Methods: C57BL6 mice were subjected to 5 minutes of thoracic aortic ischemia followed by reperfusion for up to 48 hours. Mice received either 300 mg/kg EP or lactated ringers (LR) at 30 minutes before ischemia and 3 hours after reperfusion. Neurologic function was assessed using an established rodent scale. Spinal cord tissue was analyzed for markers of inflammation (keratinocyte chemoattractant [KC], interleukin-6 [IL-6]), microglial activation (ionized calcium-binding adapter molecule-1 [Iba-1]), and apoptosis (Bcl-2, Box, and terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL] staining) at 24 and 48 hours after TAR. Nissl body stained motor neurons were counted in the anterior horns sections from L1-L5 segments. Results: Ninety-three percent of the LR mice developed dense delayed paralysis between 40 and 48 hours after TAR, whereas only 39% of EP mice developed delayed paralysis (P < .01). Bcl-2 expression was higher (P < .05) and Iba-1 expression was lower (P < .05) in the EP group only at 24 hours reperfusion. At 48 hours, the number of motor neurons was higher (P < .01) and the number and TUNEL-positive cells was lower (P < .001) in the EP-treated mice. EP decreased the expression of KC (P < .01) and IL-6 (P < .001) at 48 hours after TAR. Conclusions: The protection provided by EP against delayed paralysis correlated with preservation of motor neurons, higher expression of antiapoptotic molecules, decreased microglial cell activation, and decreased spinal cord inflammation EP may be a treatment for humans at risk for delayed paralysis.
引用
收藏
页码:1433 / 1443
页数:11
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