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褪黑素和硒对嗅觉感觉神经元凋亡的保护作用:一项大鼠模型研究。

Protective effects of melatonin and selenium against apoptosis of olfactory sensory neurons: A rat model study.

作者信息

Koc Sema, Cayli Sevil, Aksakal Ceyhun, Ocakli Seda, Soyalic Harun, Somuk Battal Tahsin, Yüce Salim

机构信息

Department of ENT Head and Neck Surgery, Antalya Education and Research Hospital, Antalya, Turkey.

出版信息

Am J Rhinol Allergy. 2016 May;30(3):62-6. doi: 10.2500/ajra.2016.30.4313.

DOI:10.2500/ajra.2016.30.4313
PMID:27216337
Abstract

BACKGROUND

Selenium plays a role in the prevention of oxidative damage and has been linked to regulatory functions in cell growth, apoptosis, cell survival, and cytotoxicity. Melatonin has an antioxidant effect, which protects against a number of free radical species. Given its antioxidant properties, melatonin has been widely known to inhibit neuronal apoptosis. We examined the cytoprotective effects of melatonin and selenium in rat olfactory sensory neurons after rhinosinusitis by immunohistochemical evaluation of olfactory bulb mucosa.

METHODS

Rhinosinusitis was induced bilaterally in 24 animals. Twenty-four rats were randomly divided into three equal groups. The melatonin group was treated with intraperitoneal (i.p.) melatonin and ampicillin-sulbactam, the selenium group was treated with i.p. selenium and ampicillin-sulbactam, the antibiotic group was treated with i.p. ampicillin-sulbactam; all three groups were treated for 10 days. After a period of 10 days of treatment, the animals were killed for immunohistochemical analyses. All olfactory bulb mucosae were removed immediately.

RESULTS

No histochemical differences were found in the three groups. Terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling-positive cells were detected in each group. In the antibiotic group, the appearance of apoptotic cells was higher, whereas the number of apoptotic cells significantly decreased in the melatonin group. When compared with the selenium group, fewer terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling-positive cells were observed in the melatonin group, which was not significant. In the antibiotic group, the cytoplasmic active caspase-3 and Bax immunostaining in the olfactory epithelium and glandular cells of stroma were higher when compared with the immunostaining in melatonin and selenium groups. Active caspase-3 and Bax immunostaining in the subepithelial stroma was dramatically reduced in the melatonin group. In contrast, the staining intensity and the number of Bcl-2 immunopositive cells were significantly increased in the melatonin group. In the selenium group, Bax and active caspase-3 were moderately immunopositive in the epithelium and subepithelial stroma. However, Bcl-2 immunostaining was more pronounced in the olfactory epithelium and some stromal cells.

CONCLUSION

Our results indicated the possibility that the supplementation of melatonin and selenium, two antioxidant agents for the treatments in the rhinosinusitis rat model, might be reduced or prevent anosmia.

摘要

背景

硒在预防氧化损伤中发挥作用,并与细胞生长、凋亡、细胞存活和细胞毒性的调节功能有关。褪黑素具有抗氧化作用,可抵御多种自由基。鉴于其抗氧化特性,褪黑素一直被广泛认为可抑制神经元凋亡。我们通过对嗅球黏膜进行免疫组化评估,研究了褪黑素和硒对鼻窦炎大鼠嗅感觉神经元的细胞保护作用。

方法

对24只动物双侧诱导鼻窦炎。将24只大鼠随机分为三组,每组数量相等。褪黑素组腹腔注射褪黑素和氨苄西林-舒巴坦,硒组腹腔注射硒和氨苄西林-舒巴坦,抗生素组腹腔注射氨苄西林-舒巴坦;三组均治疗10天。治疗10天后,处死动物进行免疫组化分析。立即取出所有嗅球黏膜。

结果

三组之间未发现组织化学差异。每组均检测到末端脱氧核苷酸转移酶介导的dUTP缺口末端标记阳性细胞。抗生素组凋亡细胞出现率较高,而褪黑素组凋亡细胞数量显著减少。与硒组相比,褪黑素组观察到的末端脱氧核苷酸转移酶介导的dUTP缺口末端标记阳性细胞较少,但差异不显著。抗生素组嗅上皮和基质腺细胞中细胞质活性半胱天冬酶-3和Bax免疫染色高于褪黑素组和硒组。褪黑素组上皮下基质中活性半胱天冬酶-3和Bax免疫染色显著降低。相反,褪黑素组中Bcl-2免疫阳性细胞的染色强度和数量显著增加。在硒组中,上皮和上皮下基质中Bax和活性半胱天冬酶-3呈中度免疫阳性。然而,Bcl-2免疫染色在嗅上皮和一些基质细胞中更为明显。

结论

我们的结果表明,在鼻窦炎大鼠模型中,补充褪黑素和硒这两种抗氧化剂可能会减轻或预防嗅觉丧失。

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