Lee Geun-Suk, Cho Jin-Hee, Park Chan-Soon, Jung Sang-Hee, Lee Dong-Hee, Jun Bum-Cho, Song Chang-Eun, Cho Kwang-Jae
Department of Otolaryngology-Head and Neck surgery, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea.
Auris Nasus Larynx. 2009 Jun;36(3):287-91. doi: 10.1016/j.anl.2008.08.004. Epub 2008 Nov 17.
Treatment of olfactory dysfunction is very difficult and has limited modality. Treatment with steroids has been used in patients with olfactory dysfunction but the side effects of steroid need to be weighed against its potential benefits. In the present study, the effect of systemic administration of dexamethasone and EGb 761 on damage to olfactory mucosa produced by zinc sulfate was examined. Expression of the immediate-early antigen (IEG), c-fos, in the olfactory bulb and piriform cortex was used to determine the effects of treatment.
Young adult CD1 mice (6 to 8 weeks old, male) were used. After anosmic mice were made by bilateral intranasal irrigation with 0.2 ml of 5% (0.17 M) zinc sulfate, anosmia was confirmed by a food finding test. Four groups of anosmic mice were studied: a steroid group (steroid injection group, n=12), an EGb group (EGb injection group, n=12), a steroid-EGb group (steroid and EGb injection group, n=12), and a control group (anosmic mice and no Tx. n=12). The olfactory bulb and piriform cortex of four mice in each group were obtained at 1, 2, and 3 weeks after instillation of zinc sulfate by cardiac perfusion, and immunohistochemical staining for c-fos was also performed to evaluate brain activity. In approximately 10 well-defined glomeruli of the olfactory bulb and in one side of the piriform cortex, c-fos (+) cells were counted. Statistical analyses were performed by Kruskal-Wallis one-way analysis of variance (ANOVA) by rank.
In all experimental groups, c-fos (+) cells increased in a time-dependent manner. The combination treatment of steroid and EGb was the most effective and the no-treatment group the least effective 1 week later after zinc sulfate irrigation. However, 3 weeks later after zinc sulfate irrigation, there was no statistically significant differences in the number of c-fos positive cells among all 4 groups (3 treatment groups and the control group).
The combination treatment of EGb and steroid enhanced the regeneration of the olfactory pathway after olfactory mucosal injury by zinc sulfate. Our study suggests that EGb could be an effective treatment option for olfactory dysfunction.
嗅觉功能障碍的治疗非常困难且方式有限。类固醇治疗已应用于嗅觉功能障碍患者，但类固醇的副作用需要与其潜在益处相权衡。在本研究中，检测了全身给予地塞米松和银杏叶提取物761（EGb 761）对硫酸锌所致嗅觉黏膜损伤的影响。通过检测嗅球和梨状皮质中即刻早期抗原（IEG）c-fos的表达来确定治疗效果。
使用年轻成年CD1小鼠（6至8周龄，雄性）。通过双侧鼻内灌注0.2 ml 5%（0.17 M）硫酸锌使小鼠嗅觉丧失，通过食物寻找试验确认嗅觉丧失。研究四组嗅觉丧失的小鼠：类固醇组（类固醇注射组，n = 12）、EGb组（EGb注射组，n = 12）、类固醇-EGb组（类固醇和EGb注射组，n = 12）和对照组（嗅觉丧失小鼠且未治疗，n = 12）。在硫酸锌滴注后1、2和3周，通过心脏灌注获取每组四只小鼠的嗅球和梨状皮质，并进行c-fos免疫组织化学染色以评估脑活动。在嗅球约10个界限清晰的肾小球和梨状皮质的一侧，对c-fos（+）细胞进行计数。采用Kruskal-Wallis秩和单向方差分析进行统计分析。
在所有实验组中，c-fos（+）细胞均呈时间依赖性增加。硫酸锌灌注1周后，类固醇与EGb联合治疗最有效，未治疗组最无效。然而，硫酸锌灌注3周后，所有4组（3个治疗组和对照组）中c-fos阳性细胞数量无统计学显著差异。
EGb与类固醇联合治疗可增强硫酸锌所致嗅觉黏膜损伤后嗅觉通路的再生。我们的研究表明，EGb可能是治疗嗅觉功能障碍的有效选择。
