外源性胰岛素样生长因子-1对大鼠局灶性脑缺血再灌注损伤的改善作用

Protective effect of insulin-like growth factor-1 on focal cerebral ischemia-reperfusion in rats

目的探讨胰岛素样生长因子-1(IGF-1)对大鼠局灶性脑缺血再灌注损伤的改善作用及其脑保护机制。方法36只大鼠随机分为3组假手术组、模型组和IGF-1组,每组12只。模型组和IGF-1组采用线栓法建立大鼠局灶性脑缺血再灌注损伤模型,假手术组除不插线外其余步骤同模型组。IGF-1组于缺血2h再灌注1h后经尾静脉注入5mg/LIGF-11ml,假手术组和模型组同时经尾静脉注入1ml生理盐水。脑缺血再灌注24h后,各组取6只大鼠灌注,取视交叉前后各2mm的脑组织,光镜下观察病理改变,免疫组化法测nNOS阳性表达。另6只断头取脑,TTC染色测脑梗死体积。结果光镜下观察,假手术组大鼠脑组织结构无明显变化。模型组大鼠皮层少见正常神经细胞,神经细胞减少,有大量淋巴细胞浸润;损伤神经元空泡变性多而明显。与模型组相比,IGF-1组皮层神经元细胞空泡变性较少,程度较轻;正常细胞增多,可见少数淋巴细胞浸润。假手术组未发生脑梗死。IGF-1组脑梗死体积百分比为(12.4±0.9)%,较模型组的(24.6±3.7)%减小(t=9.97,P<0.01)。模型组、IGF-1组和假手术组大鼠脑皮层nNOS阳性细胞数依次为(38.83±2.92),(28.33±2.58)和(15.00±1.41),逐渐降低(F=106.8,P<0.05)。结论外源性IGF-1对大鼠局灶性脑缺血再灌注损伤有保护作用,该作用可能与抑制nNOS的上调有关。

Aim ： To evaluate the protective effect of insulin-like growth factor-1 （ IGF-1 ） on focal cerebral ischemia reperfusion in rats. Methods： The rats in model group and IGF-1 group were established focal cerebral ischemia reperfusion model with suture emboli method. Then the rats in sham operation group and model group were injected normal saline and IGF-1 group was injected IGF-1 via tail vein. Brain tissue of some rats were used to observe nerve cell injury under light microscope after HE staining, and brain tissue of other rats were removed for TTC staining. Positive neurons of nNOS were observed by immunohistochemical method. Results： Compared with the model group, the injury degree of neuron greatly reduced and the infarction volume also markedly decreased in the IGF-1 group （ P 〈0. 01 ）. At the same time, the number of nNOS positive neuron dropped significantly in the IGF-1 group compared with model group （ P 〈 0.01）. Conclusion： IGF-1 plays a protective role in rat focal cerebral ischemia-reperfusion injury. The nervous protective mechanism of IGF-1 may involve in decreasing nNOS activity.