Department of Physiology and Pharmacology, Zanjan University of Medical Sciences, Iran.
Cell Mol Neurobiol. 2011 Jul;31(5):765-73. doi: 10.1007/s10571-011-9682-5. Epub 2011 Apr 12.
The present work was designed to investigate the potential protective effects of post-ischemic treatment with aminoguanidine (AG) on sciatic nerve ischemia/reperfusion (I/R) injury in rat. Seventy-two rats were divided into 12 groups (n = 6). We used ischemia model in these groups by occluding the right common iliac and femoral arteries for 3 h with a silk suture 6-0 using slipknot technique. Treatment groups (2, 4, 6, 8, 10, and 12) received 150 mg/kg AG intraperitoneally 24 h after induction of ischemia. After certain time intervals of reperfusion (2, 4, 7, 14, and 28 days), the function of the hind limb was assessed using behavioral scores based on gait, racing reflex, toe spread, pinch sensitivity, paw position, and grasp. After euthanasia, sciatic nerves were removed at the end of reperfusion times and sections were cut at 5 μm, then were stained for light microscopy studies and graded for ischemic fiber degeneration (IFD), edema, and apoptosis. Maximal behavioral deficit occurred at 7 days of reperfusion. The comparison of behavioral score pertaining to the control and AG groups revealed significant differences and showed also a better time course in recovery (P < 0.05). Other than 3 and 4 groups, the amount of edema in AG treatment groups showed significant differences compared with control groups (P < 0.05). IFD was also significantly decreased in the AG treatment groups than controls. Most importantly, I/R-induced apoptosis were improved significantly on the 4th, 7(th), and 14th days of reperfusion in AG-treated groups compared to controls. In conclusion, our findings suggest that post-ischemic administration of AG exhibits protective effect against sciatic nerve I/R injury.
本研究旨在探讨缺血后给予氨基胍(AG)治疗对大鼠坐骨神经缺血/再灌注(I/R)损伤的潜在保护作用。72 只大鼠随机分为 12 组(每组 6 只)。采用丝线 6-0 滑结技术结扎右侧股总动脉和髂动脉 3 h 构建缺血模型。造模 24 h 后,治疗组(2、4、6、8、10 和 12 组)给予 150 mg/kg AG 腹腔注射。再灌注不同时间(2、4、7、14 和 28 d)后,采用行为评分评估后肢功能,评分基于步态、赛跑反射、趾间距、触压觉、足位和抓握。再灌注结束时取出坐骨神经,每隔 5 μm 取一段组织切片,进行光镜研究并对缺血性纤维变性(IFD)、水肿和凋亡进行分级。再灌注 7 d 时出现最大行为缺陷。与对照组相比,AG 组的行为评分差异有统计学意义,且恢复情况更好(P < 0.05)。AG 治疗组与对照组相比,除 3 和 4 组外,其他组的水肿程度差异有统计学意义(P < 0.05)。AG 治疗组的 IFD 也明显低于对照组。更重要的是,AG 治疗组在再灌注第 4、7 和 14 天的 I/R 诱导的凋亡明显减少。综上所述,本研究结果表明,缺血后给予 AG 可对坐骨神经 I/R 损伤产生保护作用。