姜黄素对自发性高血压大鼠海马缺血/再灌注损伤神经元凋亡核通路的影响

目的:探讨自发性高血压大鼠(SHR)脑缺血/再灌注损伤海马神经元凋亡c-Jun氨基末端激酶(JNK)核通路的变化特点,以及姜黄素对其保护作用可能机制。方法:雄性Wistar-Kyoto大鼠(WKY)和SHR,随机分为5组:WKY假手术组(W-Sham组)、缺血/再灌注组(W-I/R组)和SHR假手术组(S-Sham组)、缺血/再灌注组(S-I/R组)、姜黄素100mg/kg预处理组(S-Cur组),上述5个实验组按再灌注时间又分为再灌注2h、6h、1d、3d、7d5个亚组(n=6)。采用四动脉结扎法制备脑缺血/再灌注模型,以TUNEL法检测海马CA1区的细胞凋亡,免疫组化法分析海马CA1区c-jun、c-fos的动态变化。结果:S-Sham组大鼠海马CA1区TUNEL细胞数量和c-jun、c-fos表达高于W-Sham组(P0.05),S-I/R组TUNEL细胞数量和c-jun、c-fos表达高于S-Sham组及W-I/R组(P0.05);S-Cur组TUNEL细胞数量和c-jun、c-fos表达较S-I/R组明显降低(P0.05)。结论:缺血/再灌注更易导致SHR海马神经元凋亡。姜黄素可抑制SHR脑缺血/再灌注损伤海马神经元凋亡,其作用机制可能与抑制c-jun、c-fos蛋白的表达有关。

Effect of curcumine on the nuclear pathway of JNK during hippocampal ischemia/reperfusion injury in SHR

Objective：To investigate the diversify of the nuclear pathway of c-Jun NH2-terminal kinases（JNK） during transient brain ischemia/reperfusion injury in hippocampal neuron apoptosis in spontaneously hypertensive rats（SHR） and to test whether the neuroprotection of curcumine on transient brain ischemia/reperfusion injury in SHR is related to the nuclear pathway of JNK. Methods： Male Wistar-Kyoto（WKY）rats and SHR were randomly divided into five groups（n=6）： WKY sham group（W-Sham）,WKY ischemia/reperfusion group（W-I/R）,SHR sham group（S-Sham）,SHR ischemia/reperfusion group（S-I/R） and SHR curcumine （a chinese traditional medicine）100 mg/kg treatment group（S-Cur）,which were sacrificed at 2 h,6 h,24 h,3 d and 7 d after reperfusion. Global brain ischemic model was established by 4-VO method.The TdT-mediated dUTP nick end labeling（TUNEL） method was used to detect the neuron apoptosis in hippocampal CA1 region.The immunohistochemical method was applied to investigate the expressions of c-jun and c-fos in hippocampal CA1 region. Results： The expressions of apoptosis and c-jun and c-fos in CA1 region in S-Sham group,W-I/R group and S-I/R group were more than those in W-Sham group（P0.05）,were significantly increased in S-I/R group than those in W-I/R group（P0.05）,and were significantly decreased in S-Cur group than those in S-I/R group（P0.05）. Conclusion： Neuronal apoptosis and the expressions of c-jun and c-fos are more in SHR hippocampal. Global brain ischemia /reperfusion injury induces more expressions of apoptosis in hippocampal neuron in SHR,and the more expressions of c-jun and c-fos may participate in that process. The neuroprotection of curcumine in SHR is related to c-jun and c-fos.