肢体缺血后处理对糖尿病大鼠局灶性脑缺血再灌注损伤的影响

Effects of postconditioning with leg ischemia on focal cerebral ischemia-reperfusion injury in diabetic rats

目的评价肢体缺血后处理对糖尿病大鼠局灶性脑缺血再灌注损伤的影响。方法腹腔注射链脲佐菌素制备大鼠糖尿病模型，造模成功的雄性SD大鼠40只，随机分为4组（n=10）：对照组（C组）；假手术组（S组）仅暴露颈动脉；缺血再灌注组（IR组）线栓阻断大脑中动脉1．5h，再灌注6h；肢体缺血后处理组（IC组）阻断大脑中动脉1．5h，再灌注前30min时捆绑双下肢5min，松开5min，反复3次后恢复灌注，于脑再灌注6h时行神经行为学评分后断头处死大鼠取脑，采用TYC染色法测定脑梗死体积，计算脑梗死体积百分比，TUNEL法检测凋亡神经元，计算神经元凋亡率。结果与C组和S组比较，IR组和IC组再灌注6h时神经行为学评分、脑梗死体积百分比及神经元凋亡率明显升高（P〈0．01）；与IR组比较，IC组再灌注6h时神经行为学评分差异无统计学意义（P〉0．05），脑梗死体积百分比及神经元凋亡率明显降低（P〈0．05或0．01）。结论肢体缺血后处理可减轻糖尿病大鼠局灶性脑缺血再灌注损伤。

Objective To evaluate the effects of leg ischemic postconditioning on focal cerebral ischemiareperfusion （I/R） injury in diabetic rats. Methods Forty male diabetic SD rats weighing 270-320 g were randomly assigned to one of 4 groups （n = 10 each）： group Ⅰ Control （C）; group Ⅱ sham operation （S）; group Ⅲ focal cerebral ischemia-reperfusion （I/R） and group Ⅳ leg ischemic postconditioning （IPC）. Diabetes mellitus was induced by intraperitoneal streptozotocin. Local cerebral I/R was produced by middle cerebral artery occlusion （MCAO） for 1.5 h followed by 6 h reperfusion. A nylon thread with rounded tip was inserted into internal carotid artery and threaded cranially until resistance was felt. Leg ischemia was induced by placing tourniquet on both legs at 30 min before reperfusion. The animals underwent 3 episodes of 5 min leg ischemia at 5 min intervals. Neurofunctional deficit was assessed and recorded at the end of 6h reperfusion using neurologic deficit scores （NDS） （0 = no deficit, 4 = unable to crawl and semiconscious）. The animals were then decapitated and their brains were removed for determination of volume of cerebral infarct （by TIC staining） and ratio of neuronal apoptosis （by TUNEL）. Results NDS and cerebral infarct volume were significantly increased at the end of 6 h reperfusion in group I/R and IPC as compared with group C and S. IPC significantly decreased cerebral infarct volume and ratio of neuronal apoptosis induced by MCAO. There was no significant diffei＇ence in NDA between group I/R and IPC. Conclusion Leg ischemic postconditioning can protect the brain against focal cerebral I/R injury in diabetic rats.