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姜黄素通过抑制促炎细胞因子改善脑缺血再灌注大鼠受损的工作记忆

[Curcumin improves the impaired working memory in cerebral ischemia-reperfusion rats by inhibiting proinflammatory cytokines].

作者信息

Ji Bin, Han Yuan, Liu Qixing, Liu Xuhua, Yang Fanghua, Zhou Rui, Lian Qingquan, Cao Hong, Li Jun

机构信息

Department of Anesthesiology, Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, China.

Department of Anesthesiology, Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, China. Email:

出版信息

Zhonghua Yi Xue Za Zhi. 2014 Apr 8;94(13):1029-33.

PMID:24851695
Abstract

OBJECTIVE

To investigate the ameliorative effect of curcumin pretreatment against impaired spatial working memory on global cerebral ischemia-reperfusion rats and to explore its mechanism.

METHODS

After trained on a modified T-maze, 120 adult SD rats were randomly divided into 5 groups: sham group (S group), cerebral ischemia-reperfusion group (IR group), curcumin group (C group), LPS group (L group) and curcumin+LPS group (C+L group). Rats were treated with drugs or vehicles 1 h before 10 min global cerebral ischemia. Six rats in each group 7 days after reperfusion were tested in T-maze. Six rats in each group were sacrificed at 2 h, 1, 3 and 7 d after reperfusion and their serum or brains were harvested. Brain sections were stained with HE or toluidine blue and neuronal damage was quantified by the average neuronal density of CA1 area. Immunohistochemical staining for hippocampal IL-1β and TNF-α was carried out, levels of serum IL-1β and TNF-α was detected using ELISA procedure.

RESULTS

Compared with S group, percentage of T-maze correct responses was decreased (88% ± 12% vs 69% ± 8%, P < 0.05), an extensive pyramidal neurons loss in CA1 area was observed, level of IL-1β (0.26 ± 0.04 vs 0.53 ± 0.06, P < 0.05;48 ± 13 vs 161 ± 31, P < 0.05) and TNF-α (40.244 ± 0.025 vs 0.418 ± 0.036, P < 0.05; 33 ± 4 vs 85 ± 15, P < 0.05) in hippocampi or serum was increased in IR group. Compared with IR group, percentage of T-maze correct responses was increased (78% ± 13%) and average pyramidal neuronal density in CA1 area was increased with an decrease in hippocampi or serum IL-1β (0.44 ± 0.09, 72 ± 19) and TNF-α (0.307 ± 0.047, 57 ± 14) in C group(P < 0.05). Compared with IR group, percentage of T-maze correct responses (61% ± 6%) was decreased with IL-1β (0.86 ± 0.13, 331 ± 51), TNF-α (0.735 ± 0.059, 185 ± 20) in hippocampi and serum was increased in L group (P < 0.05). Compared with L group, percentage of T-maze correct responses (69% ± 12%) and average pyramidal neuronal density in CA1 area was increased with IL-1β (0.69 ± 0.09, 246 ± 24), TNF-α(0.586 ± 0.047, 105 ± 25) in hippocampi and serum was decreased in C+L group (P < 0.05).

CONCLUSION

Curcumin pretreatment improves the impaired spatial working memory in global cerebral ischemia-reperfusion rats by inhibiting proinflammatory cytokines.

摘要

目的

探讨姜黄素预处理对全脑缺血再灌注大鼠空间工作记忆障碍的改善作用及其机制。

方法

120只成年SD大鼠在改良T迷宫训练后,随机分为5组:假手术组(S组)、脑缺血再灌注组(IR组)、姜黄素组(C组)、脂多糖组(L组)和姜黄素+脂多糖组(C+L组)。在全脑缺血10分钟前1小时,对大鼠进行药物或溶剂处理。再灌注7天后,每组6只大鼠在T迷宫中进行测试。再灌注后2小时、1天、3天和7天,每组处死6只大鼠,采集血清或脑组织。脑切片进行HE或甲苯胺蓝染色,通过CA1区平均神经元密度对神经元损伤进行定量。进行海马IL-1β和TNF-α的免疫组织化学染色,采用ELISA法检测血清IL-1β和TNF-α水平。

结果

与S组相比,IR组T迷宫正确反应百分比降低(88%±12%对69%±8%,P<0.05),CA1区可见广泛的锥体细胞丢失,海马或血清中IL-1β(0.26±0.04对0.53±0.06,P<0.05;48±13对161±31,P<0.05)和TNF-α(40.244±0.025对0.418±0.036,P<0.05;33±4对85±15,P<0.05)水平升高。与IR组相比,C组T迷宫正确反应百分比升高(78%±13%),CA1区锥体细胞平均密度增加,海马或血清中IL-1β(0.44±0.09,72±19)和TNF-α(0.307±0.047,57±14)降低(P<0.05)。与IR组相比,L组T迷宫正确反应百分比降低(61%±6%),海马和血清中IL-1β(0.86±0.13,331±51)、TNF-α(0.735±0.059,185±20)升高(P<0.05)。与L组相比,C+L组T迷宫正确反应百分比(69%±12%)和CA1区锥体细胞平均密度增加,海马和血清中IL-1β(0.69±0.09,246±24)、TNF-α(0.586±0.047,105±25)降低(P<0.05)。

结论

姜黄素预处理通过抑制促炎细胞因子改善全脑缺血再灌注大鼠受损的空间工作记忆。

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