Huang Sheng, Wang Bin, Zhang Zhan-qin, Meng Zhi-yan, Cao Hong, Lian Qing-quan, Li Jun
Department of Anesthesiology, Second Affiliated Hospital, Wenzhou Medical College, China.
Zhonghua Yi Xue Za Zhi. 2011 May 24;91(19):1340-3.
To explore the effects of curcumin on the expression of high mobility group box 1 (HMGB1) and apoptotic neurons in hippocampus after global cerebral ischemia/reperfusion in SD rats.
A total of 192 male SD rats were randomly divided into 4 groups: sham group (SH), ischemia-reperfusion group (IR), curcumin group (Cur) and solvent control group (SC). Bilateral vertebrate arteries were electrocauterized and bilateral common carotid arteries liberated in 3 ischemic groups. Isasteric curcumin solutions (200 mg/kg) or menstruum were injected intraperitoneally at 1 hour pre-ischemia in Cur and SC groups. The rats in each group were ligated for 15 minutes and then decapitated at 1, 3, 5 and 7 d post-reperfusion respectively. Cell morphology was observed on hematoxylin & eosin-stained slides. Apoptotic neurons were detected in CA1 region by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling). Western blot was used to make a semi-determination of HMGB1 expression.
At each time point, the number of apoptotic neurons was much more in IR and SC groups than that in SH group (P < 0.05). And the number of apoptotic neurons at 1, 3, 5, 7 d post-reperfusion was only 41%, 57%, 65% and 70% in Cur group respectively (P < 0.05). The expressional level of HMGB1 in IR and SC groups was significantly lower at 1d post-reperfusion (0.685 ± 0.050; 0.695 ± 0.053 vs 0.977 ± 0.063, P < 0.05). And it was significantly higher at 3, 5, 7 d post-reperfusion in IR and SC groups than that in SH groups (1.360 ± 0.045/1.353 ± 0.045; 1.342 ± 0.046/1.338 ± 0.047; 1.319 ± 0.052/1.322 ± 0.035 vs 0.992 ± 0.031; 0.978 ± 0.090; 0.992 ± 0.075, P < 0.05). The level at 1 d post-reperfusion (0.842 ± 0.063) in Cur group was significantly higher than that in IR and SC groups but lower than that in SH group. And it was lower at 3, 5, 7 d post-reperfusion (1.125 ± 0.023, 1.098 ± 0.073, 1.087 ± 0.089) than those in IR and SC groups (P < 0.05). There was no significant difference of HMGB1expression level between IR and SC groups.
The expression level of HMGB1 in hippocampus is significantly reduced at 1 d post-reperfusion. Then it significantly increases and a high level is maintained until 7 d after global cerebral ischemia/reperfusion. Curcumin can reduce hippocampal neuronal apoptosis and injury. Such an effect may be due to an inhibition of the synthesis and release of HMGB1.
探讨姜黄素对SD大鼠全脑缺血/再灌注后海马区高迁移率族蛋白B1（HMGB1）表达及凋亡神经元的影响。
将192只雄性SD大鼠随机分为4组：假手术组（SH）、缺血再灌注组（IR）、姜黄素组（Cur）和溶剂对照组（SC）。对3个缺血组大鼠进行双侧椎动脉电凝并游离双侧颈总动脉。Cur组和SC组在缺血前1小时腹腔注射姜黄素溶液（200mg/kg）或溶剂。每组大鼠结扎15分钟后，分别在再灌注后1、3、5和7天断头。苏木精-伊红染色切片观察细胞形态。采用末端脱氧核苷酸转移酶介导的dUTP生物素缺口末端标记法（TUNEL）检测CA1区凋亡神经元。采用蛋白质免疫印迹法半定量检测HMGB1表达。
各时间点，IR组和SC组凋亡神经元数量均显著多于SH组（P<0.05）。Cur组再灌注后1、3、5、7天凋亡神经元数量分别仅为IR组和SC组的41%、57%、65%和70%（P<0.05）。IR组和SC组再灌注后1天HMGB1表达水平显著低于SH组（0.685±0.050；0.695±0.053比0.977±0.063，P<0.05）。IR组和SC组再灌注后3、5、7天HMGB1表达水平显著高于SH组（1.360±0.045/1.353±0.045；1.342±0.046/1.338±0.047；1.319±0.052/1.322±0.035比0.992±0.031；0.978±0.090；0.992±0.075，P<0.05）。Cur组再灌注后1天HMGB1表达水平（0.842±0.063）显著高于IR组和SC组，但低于SH组。再灌注后3、5、7天Cur组HMGB1表达水平（1.125±0.023，1.098±0.073，1.087±0.089）低于IR组和SC组（P<0.05）。IR组和SC组HMGB1表达水平差异无统计学意义。
全脑缺血/再灌注后1天海马区HMGB1表达水平显著降低，随后显著升高并维持在较高水平直至7天。姜黄素可减少海马神经元凋亡和损伤。这种作用可能是由于抑制了HMGB1的合成和释放。
