丁苯酞预处理对缺血再灌注损伤后大鼠海马神经元的保护作用

Protective effects of 3-n-butylphthalide pretreatment on hippocampal neurons of rats after cerebral ischemia reperfusion injury

目的探讨丁苯酞(NBP)预处理对脑缺血再灌注损伤后大鼠海马神经元的保护作用。方法将120只SD大鼠随机分为假手术组、缺血再灌注组、NBP低剂量预处理组(低剂量组)、NBP中剂量预处理组(中剂量组)和NBP高剂量预处理组(高剂量组),每组24只大鼠。低、中、高剂量组大鼠分别给予20 mg/kg、40 mg/kg、80 mg/kg NBP预处理。采用改良Zea Longa线栓法制备脑缺血再灌注模型。2%氯化三苯基四氮唑(TTC)染色测量梗死体积,免疫组织化学法观察5-羟色胺(5-HT)阳性细胞数,免疫印迹法检测5-HT蛋白水平。结果 NBP低剂量组、中剂量组、高剂量组脑梗死体积显著小于缺血再灌注组(均P<0.05)。中剂量组与高剂量组脑梗死体积显著小于低剂量组(均P<0.05)。与假手术组比较,缺血再灌注组大鼠海马中5-HT阳性细胞数及蛋白表达明显降低(均P<0.01)。与缺血再灌注组比较,NBP低、中、高剂量组的5-HT阳性细胞数及蛋白表达显著增加(均P<0.05)。中剂量组与高剂量组5-HT阳性细胞数及蛋白表达显著高于低剂量组(均P<0.05),高剂量组与中剂量组差异无统计学意义。结论丁苯酞预处理具有脑保护作用,其机制可能为上调缺血海马半暗带区5-HT表达。

Objective To explore the protective effects of 3-n-butylphthalide（ NBP） pretreatment on the hippocampus neurons of rats afer cerebral ischemia reperfusion injury. Methods One hundred and twenty SD rats were randomly divided into sham group,ischemia-reperfusion（ IR） group,low dosage NBP pretreatment group（ low dosage group）,middle dosage NBP pretreatment group（ middle dosage group） and high dosage NBP pretreatment group（ high dosage group）,each group had 24 rats. Low dosage group,middle dosage group and high dosage group were respectively given NBP 20 mg / kg,40 mg / kg and 80 mg / kg. The right middle cerebral artery occlusion focal ischemia reperfusion rat models were established with the improved Longa-Zea method. The volume of cerebral infarction was identified with 2% triphenyl tetrazolium chloride（ TTC） staining; immunohistoche-mistry was used to observe the expression of 5-hydroxytryptamine（ 5-HT）; the protein expression of the 5-HT was measured by Western blotting. Results The volume of cerebral infarction in low dosage group,middle dosage group and high dosage group were significantly smaller than that in IR group（ all P〈0. 05）. The volume of cerebral infarction in middle dosage group and high dosage group were significantly smaller than that in low dosage group（ all P〈0. 05）. Compared with sham group,the number of 5-HT positive cells of and protein expression in IR group was significantly decreased（ P〈0. 01）. Compared with IR group,the number of 5-HT positive cells of and protein expression in low dosage group,middle dosage group and high dosage group were significantly increased（ all P〈0. 05）. The number of 5-HT positive cells of and protein expression in middle dosage group and high dosage group were significantly increased than those in low dosage group（ all P〈0. 05）,and there was no statistical significance between middle dosage group and high dosage group. Conclusion NBP pretreatment has cerebral protection,the mechanism may be significantly upregulated the expression of 5-HT in ischemic foci in hippocampus.