Lang-Lazdunski L, Heurteaux C, Vaillant N, Widmann C, Lazdunski M
Department of Cardiovascular Surgery, Paris, and the Institute of Molecular and Cellular Pharmacology, Valbonne, France.
J Thorac Cardiovasc Surg. 1999 May;117(5):881-9. doi: 10.1016/S0022-5223(99)70367-3.
Recent studies support the involvement of glutamate neurotoxicity in the pathophysiology of spinal cord injury induced by aortic crossclamping. We investigated the effects of riluzole, a neuroprotective drug that blocks glutamatergic neurotransmission, in a rabbit model of spinal cord ischemia.
The infrarenal aortas of New Zealand White albino rabbits (n = 40) were occluded for 40 minutes. Experimental groups were as follows: sham operation group (n = 5), control group undergoing occlusion but receiving no pharmacologic intervention (n = 10), experimental group A (n = 10) receiving 8 mg/kg riluzole intravenously 30 minutes before ischemia, experimental group B (n = 10) receiving 4 mg/kg riluzole intravenously 30 minutes before ischemia and at the onset of reperfusion, and experimental group C (n = 10) receiving 8 mg/kg riluzole intravenously at the onset of reperfusion. Neurologic status was assessed at 6, 24, and 48 hours after the operation and then daily until the fifth day. All animals were killed at 24, 48, or 120 hours after the operation. Spinal cords were harvested for histopathologic studies, immunohistochemical studies for microtubule-associated protein 2, and search for morphologic features of apoptosis by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining method.
All animals in the control group became paraplegic. Except for 1 rabbit in group C, all riluzole-treated animals had better neurologic function. Luxol fast blue and terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining methods demonstrated typical morphologic changes characteristic of necrosis and apoptosis in control animals. Riluzole prevented or attenuated ischemia-induced necrosis, apoptosis, and cytoskeletal proteolysis, depending on the dose and the timing of administration.
Riluzole may have therapeutic utility during high-risk operations on the thoracoabdominal aorta.
近期研究支持谷氨酸神经毒性参与主动脉交叉钳夹所致脊髓损伤的病理生理过程。我们在兔脊髓缺血模型中研究了利鲁唑（一种阻断谷氨酸能神经传递的神经保护药物）的作用。
将新西兰白兔（n = 40）的肾下腹主动脉阻断40分钟。实验组如下：假手术组（n = 5），接受阻断但未接受药物干预的对照组（n = 10），在缺血前30分钟静脉注射8 mg/kg利鲁唑的实验组A（n = 10），在缺血前30分钟及再灌注开始时静脉注射4 mg/kg利鲁唑的实验组B（n = 10），以及在再灌注开始时静脉注射8 mg/kg利鲁唑的实验组C（n = 10）。术后6、24和48小时评估神经功能状态，然后每天评估直至第5天。所有动物在术后24、48或120小时处死。取脊髓进行组织病理学研究、微管相关蛋白2的免疫组化研究，并通过末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸生物素缺口末端标记染色法寻找凋亡的形态学特征。
对照组所有动物均发生截瘫。除C组1只兔外，所有接受利鲁唑治疗的动物神经功能均较好。卢戈氏固绿和末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸生物素缺口末端标记染色法显示对照组动物有典型的坏死和凋亡形态学改变。利鲁唑根据给药剂量和时间可预防或减轻缺血诱导的坏死、凋亡和细胞骨架蛋白水解。
利鲁唑在胸腹主动脉高危手术中可能具有治疗作用。
