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艾地苯醌和皮质类固醇治疗对大鼠甲醇诱导的中毒性视神经和视网膜损伤的影响:生化和组织病理学检查

The effect of idebenone and corticosteroid treatment on methanol-induced toxic optic nerve and retinal damage in rats: biochemical and histopathological examination.

作者信息

Nalcacioglu Pinar, Kavuncu Sevim, Taskin Turkmenoglu Tugba, Sonmez Cigdem Atay

机构信息

Department of Ophthalmology, Ankara Yildirim Beyazit University, Ankara, Turkey.

Ankara Ulucanlar Eye Research and Training Hospital, Ankara, Turkey.

出版信息

Cutan Ocul Toxicol. 2022 Sep;41(3):250-256. doi: 10.1080/15569527.2022.2106994. Epub 2022 Aug 5.

Abstract

PURPOSE

To evaluate the therapeutic effects of methylprednisolone, the CoenzymeQ10 (CoQ10) structural analogue idebenone, and both together on the optic nerve (ON) and retinal layers following methanol intoxication in rats with histopathological and biochemical methods.

MATERIALS AND METHODS

This experimental study was conducted with 30 male Wistar rats. The rats were divided into five equal groups depending on the treatment protocol:healthy controls (HC), methanol (M), methanol + methylprednisolone (MM), methanol + idebenone (MI), and methanol + methylprednisolone + idebenone (MMI).Distilled water was provided orally to the HC group, while 20% methanol was administered orally at a dose of 3 g/kg with a nasogastric tube to all rats in groups except the HC group. Four hours later, group MM received 1 mg/kg of intraperitoneal methylprednisolone for 10 days using an insulin syringe, and group MI received 20 mg/kg idebenone by nasogastric catheter for 28 days. MMI group was administered oral idebenone and intraperitoneal methylprednisolone at the same dose. Serum samples were obtained on the 28 day for biochemical analysis and afterwards the rats were euthanized for histopathological examination and eyes were enucleated. ON was evaluated for circumference thickness, vascularization and number of astrocytes, also retinal layers were examined for structural changes by histopathological examination.

RESULTS

Comparison of the antioxidant and oxidative stress biomarkers between the groups revealed no statistically significant difference ( > 0.05). By histopathological evaluation the most marked results were obtained by MMI group with an improvement of all parameters mentioned. There was no statistically significant difference between MM group and M group for RD score ( = 0.123). In addition, ON vacuolization in MI group ( < 0.001) and ON astrocyte increase in both MI and MMI groups were statistically significantly lower than in M group ( = 0.001,  = 0.001, respectively).

CONCLUSIONS

The early use (within hours) of idebenone and short-term methylprednisolone treatment together may protect against the retinal and ON damage developing after methanol ingestion in rats as guided by the histopathological data.

摘要

目的

采用组织病理学和生物化学方法,评估甲基强的松龙、辅酶Q10(CoQ10)结构类似物艾地苯醌以及二者联合应用对甲醇中毒大鼠视神经(ON)和视网膜各层的治疗效果。

材料与方法

本实验研究选用30只雄性Wistar大鼠。根据治疗方案将大鼠分为五组,每组数量相等:健康对照组(HC)、甲醇组(M)、甲醇 + 甲基强的松龙组(MM)、甲醇 + 艾地苯醌组(MI)、甲醇 + 甲基强的松龙 + 艾地苯醌组(MMI)。HC组经口给予蒸馏水,除HC组外,其余各组大鼠均经鼻胃管以3 g/kg的剂量口服20%甲醇。4小时后,MM组使用胰岛素注射器腹腔注射1 mg/kg甲基强的松龙,持续10天;MI组经鼻胃管给予20 mg/kg艾地苯醌,持续28天。MMI组给予相同剂量的口服艾地苯醌和腹腔注射甲基强的松龙。在第28天采集血清样本进行生化分析,之后对大鼠实施安乐死以进行组织病理学检查,并摘除眼球。评估视神经的周长厚度、血管形成和星形胶质细胞数量,同时通过组织病理学检查观察视网膜各层的结构变化。

结果

各组之间抗氧化和氧化应激生物标志物的比较显示无统计学显著差异(> 0.05)。通过组织病理学评估,MMI组在所有提及参数的改善方面取得了最显著的结果。MM组和M组的视网膜脱离(RD)评分无统计学显著差异(= 0.123)。此外,MI组的视神经空泡化(< 0.001)以及MI组和MMI组的视神经星形胶质细胞增加在统计学上均显著低于M组(分别为= 0.001,= 0.001)。

结论

根据组织病理学数据,早期(数小时内)联合使用艾地苯醌和短期甲基强的松龙治疗可能预防大鼠摄入甲醇后发生的视网膜和视神经损伤。

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