毛西京　罗翔丹　于挺敏

[摘要] 目的 观察丁苯酞（NBP）对不同时间点血管性痴呆大鼠海马组织肿瘤坏死因子α（TNF-α）和白介素1β（IL-1β）表达的影响。方法 将80只健康Wistar大鼠按随机区组法分为血管性痴呆模型（VD）组、血管性痴呆模型+丁苯酞氯化钠注射液（NBP+VD）组、假手术+丁苯酞氯化钠注射液（NBP+Sham）组和假手术（Sham）组4个组，每组各20只。采用永久性双侧颈总动脉结扎法制备VD大鼠模型。NBP+Sham组和NBP+VD组大鼠术后1 d开始给予丁苯酞氯化钠注射液腹腔注射，剂量为5 mg/（kg·d），Sham组和VD组大鼠给予生理盐水腹腔注射（0.2 mL/d），各组大鼠均连续腹腔注射给药7 d，每组按时间分为术后1周、2周、4周和8周4个亚组，于不同时间点断头取脑分离海马组织。采用ELISA方法检测海马组织TNF-α和IL-1β的表达。结果 术后1、2、4、8周，VD组大鼠海马组织TNF-α和IL-1β的表达均明显高于Sham组（P < 0.05）；术后8周，NBP+VD组大鼠海马组织TNF-α的表达明显低于VD组大鼠（P < 0.05）；VD组大鼠海马组织IL-1β的表达于2周时达到高峰期（P < 0.05）。 结论 VD大鼠海马组织TNF-α和IL-1β表达增加，NBP可通过降低VD大鼠海马组织TNF-α的水平从而发挥神经保护作用。

[关键词] 丁苯酞；血管性痴呆；海马；肿瘤坏死因子α；白介素1β

[中图分类号] R743 [文献标识码] A [文章编号] 1673-7210（2017）01（c）-0012-04

[Abstract] Objective To study the effects of 3-n-butylphthalide （NBP） on the expression of TNF-α and IL-1β at different time points in the hippocampus of vascular dementia rats. Methods A total of 80 Wistar rats were assigned to vascular dementia models （VD） group， vascular dementia models + NBP injection （NBP+VD） group， sham surgery + NBP injection （NBP+Sham） group and sham surgery （sham） group by randomized blocks， with 20 rats in each group. Vascular dementia rat model was established by ligating bilateral common carotid artery. The NBP+VD group and NBP+Sham group were intraperitoneally injected with NBP 5 mg/（kg·d）， VD group and Sham group were intraperitoneally injected with 0.2 mL/d saline for 7 days. Each group was divided into four subgroups （n=5） at 1， 2， 4 and 8 weeks after surgery. The rats in each group were decapitated to obtain brains at different time points， and hippocampus were isolated. TNF-α and IL-1β expressions in the hippocampus were determined by ELISA method. Results The expressions of TNF-α and IL-1β in the hippocampus of VD group were significantly higher than those of Sham group at each time point（P < 0.05）； the expression of TNF-α in the hippocampus of NBP+VD group was significantly lower than that of VD group at 8 weeks after surgery（P < 0.05）； the expression of IL-1β in the hippocampus of VD group reached peak level at 2 weeks after surgery. Conclusion The expression of TNF-α and IL-1β increase in the hippocampus of rats with vascular dementia. NBP may exert the protective effect by reducing TNF-α level in the hippocampus of vascular dementia rats.

[Key words] 3-n-butylphthalide； Vascular dementia； Hippocampus； Tumor necrosis factor-α； Interleukin-1β

丁苯酞（3-n-butylphthalide，NBP）是人工合成的消旋正丁基苯酞，作為临床用于治疗缺血性脑卒中的国家级一类新药，NBP能够明显减轻急性缺血性脑卒中患者中枢神经功能缺损[1]。随着对NBP研究的不断深入，目前发现NBP对血管性痴呆（vascular dementia，VD）也有较为明显的改善作用[2-3]，但其作用机制还缺乏深入的研究。临床研究观察到VD患者血浆中促炎细胞因子水平明显升高，并且促炎细胞因子水平与痴呆程度呈正相关[4]。Cunningham等[5]发现，脑组织中促炎细胞因子表达增加会加速痴呆的进展。TNF-α和IL-1β是两种重要的促炎细胞因子，脑缺血后海马中TNF-α和IL-1β表达增加与VD发生密切相关[6]。……