莪术二酮对肝部分切除老年小鼠术后认知功能和海马区炎性因子表达的影响

Effects of curdione on cognitive function and expression of inflammatory factors in the hippocampus after partial hepatectomy in aged mice

目的观察莪术二酮对肝部分切除的老年小鼠术后认知功能和海马区炎性因子表达的作用。方法按文献报道方法建立肝部分切除老年小鼠模型,分为假手术组、手术组(模型组)及莪术二酮高、中、低剂量组(造模并药物干预),另设空白对照组。采用Morris水迷宫评价小鼠的认知功能,采用酶联免疫吸附法检测海马组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)的水平,Western blot检测海马中NF-κB、白介素-1β(IL-1β)、白介素-6(IL-6)及肿瘤坏死因子(TNF-α)蛋白的表达。结果手术组动物水迷宫逃逸潜伏期时间明显延长(P<0.01),穿台次数显著减少(P<0.05);与手术组相比,莪术二酮显著性缩短术后逃逸潜伏期(P<0.05),并增加穿台次数(P<0.05)。肝切除术后海马组织中SOD、CAT和GSH-Px的含量均明显降低(P<0.05),MDA含量则明显升高(P<0.01)。莪术二酮组SOD、CAT和GSH-Px的含量明显升高(P<0.05),MDA释放减少(P<0.05)。莪术二酮组的术后NF-κB、IL-1β、IL-6及TNF-α蛋白的高表达显著抑制(P<0.05)。结论莪术二酮可显著改善老年小鼠部分肝切除术后认知功能障碍,其机制可能与其通过抑制海马组织中氧化应激,抑制NF-κB激活,减少炎症细胞因子IL-1β、IL-6及TNF-α的释放有关。

Objective To explore the effects of curdione on cognitive function and expression of inflammatory factors in the hippocampus after partial hepatectomy in aged mice. Methods The animals were divided into control group, sham group, operation group, and high-, medium- and low-dose curdione groups. The model of partial hepatectomy in aged mice was established according to the method reported in literature. The levels of SOD, MDA, CAT and GSH-Px in the hippocampus were detected by enzyme-linked immunosorbent assay （ELISA）, while the expressions of NF-κB, IL-1β, IL-6 and TNF-α were measured by Western blot. Results The escape latency was significantly increased （P〈0.01）, and the number of platform-site crossovers was significantly decreased in operation group （P〈0. 05）. Compared with those in operation group, curdione significantly decreased escape latency and increased platform-site crossovers （P〈0. 05, P〈0. 05）. The levels of SOD, CAT and GSH-Px in the hippocampus were significantly decreased （P 〈0.05） and the content of MDA was significantly increased after partialhepatectomy （P〈0.01）, and these were reversed by curdione （P〈0.05, P〈0.05, respectively）. The expressions of NF-κB, IL-lP, IL-6 and TNF-α protein were significantly inhibited by curdione （P 〈 0. 05）. Conclusion Curdione can significantly improve cognitive dysfunction after partial hepatectomy in aged mice and the mechanism may be related to its inhibition of oxidative stress, inhibition of NF-KB activation and reduction of inflammatory cytokincs IL-1β, IL-6 and TNF-α in the hippocampus.