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

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• 作者：Bao-Ngoc Nguyen ; MD^a ; Hassan Albadawi ; MD^a ; Rahmi Oklu ; MD ; PhD^b ; Robert S. Crawford ; MD^a ; Mitchell P. Fink ; MD^c ; Richard P. Cambria ; MD^a ; Michael T. Watkins ; MD^a ; ^{mtwatkins@mgh.harvard.edu" class="auth_mail" title="E-mail the corresponding author}
• 刊名：Journal of Vascular Surgery
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：64
• 期：5
• 页码：1433-1443
• 全文大小：2017 K

文摘

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 anti-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, Bax, 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.