CAJ | 학술논문

目的评价姜黄素预先给药对大鼠全脑缺血再灌注后空间工作记忆的作用并探讨机制.方法成年雄性SD大鼠120只,经T迷宫训练后按随机数字表法分成5组:假手术组(S组)、脑缺血再灌注组(IR组)、姜黄素组(C组)、LPS组(L组)和姜黄素+LPS组(C+L组),每组24只.各组给予相应药物或溶剂腹腔注射,1h后全脑缺血10 min后再灌注,于再灌注7d行T迷宫检测工作记忆,于再灌注2h、1、3、7d采血清和脑组织标本,HE和Nissl染色计数海马CA1区平均锥体细胞密度,免疫组化和ELISA分别检测海马和血清白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)蛋白表达.结果与S组比较,IR组T迷宫正确率降低(88％±12％比69％±8％,P＜0.05),海马平均锥体细胞密度减少,海马和血清中IL-1β(0.26±0.04比0.53±0.06,P＜0.05;48 ±13比161±31,P＜0.05)和TNF-α(40.244±0.025比0.418±0.036,P＜0.05;33±4比85±15,P＜0.05)含量增高;与IR组比较,C组T迷宫正确率(78％±13％)增高,海马平均锥体细胞密度增高,海马和血清中IL-1β(0.44±0.09,72±19)和TNF-α(0.307 ±0.047,57±14)含量减少(P＜0.05);与IR组比较,L组T迷宫正确率(61％±6％)降低、海马平均锥体细胞密度降低、海马和血清中IL-1β(0.86±0.13,331±51)增加、TNF-α(0.735 ±0.059,185±20)含量增加(P＜0.05);与L组比较,C+L组T迷宫正确率(69％±12％)增高,海马平均锥体细胞密度增高,而海马和血清中IL-1β(0.69±0.09,246±24)降低,TNF-α(0.586 ±0.047,105±25)含量降低(P＜0.05).结论姜黄素预先给药可通过抑制炎症反应改善大鼠全脑IR后病理学变化和空间工作记忆障碍.
목적 평개강황소예선급약대대서전뇌결혈재관주후공간공작기억적작용병탐토궤제.방법 성년웅성SD대서120지,경T미궁훈련후안수궤수자표법분성5조:가수술조(S조)、뇌결혈재관주조(IR조)、강황소조(C조)、LPS조(L조)화강황소+LPS조(C+L조),매조24지.각조급여상응약물혹용제복강주사,1h후전뇌결혈10 min후재관주,우재관주7d행T미궁검측공작기억,우재관주2h、1、3、7d채혈청화뇌조직표본,HE화Nissl염색계수해마CA1구평균추체세포밀도,면역조화화ELISA분별검측해마화혈청백세포개소-1β(IL-1β)화종류배사인자-α(TNF-α)단백표체.결과 여S조비교,IR조T미궁정학솔강저(88％±12％비69％±8％,P＜0.05),해마평균추체세포밀도감소,해마화혈청중IL-1β(0.26±0.04비0.53±0.06,P＜0.05;48 ±13비161±31,P＜0.05)화TNF-α(40.244±0.025비0.418±0.036,P＜0.05;33±4비85±15,P＜0.05)함량증고;여IR조비교,C조T미궁정학솔(78％±13％)증고,해마평균추체세포밀도증고,해마화혈청중IL-1β(0.44±0.09,72±19)화TNF-α(0.307 ±0.047,57±14)함량감소(P＜0.05);여IR조비교,L조T미궁정학솔(61％±6％)강저、해마평균추체세포밀도강저、해마화혈청중IL-1β(0.86±0.13,331±51)증가、TNF-α(0.735 ±0.059,185±20)함량증가(P＜0.05);여L조비교,C+L조T미궁정학솔(69％±12％)증고,해마평균추체세포밀도증고,이해마화혈청중IL-1β(0.69±0.09,246±24)강저,TNF-α(0.586 ±0.047,105±25)함량강저(P＜0.05).결론 강황소예선급약가통과억제염증반응개선대서전뇌IR후병이학변화화공간공작기억장애.
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.Imunohistochemical staining for hippocampal IL-1β and TNF-oα 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-1β3 (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.