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远程缺血预处理对顺铂诱导的大鼠全身毒性和耳毒性的影响:肿瘤坏死因子-α和一氧化氮的作用

Effect of Remote Ischemic Preconditioning on Systemic Toxicity and Ototoxicity Induced by Cisplatin in Rats: Role of TNF-α and Nitric Oxide.

作者信息

Martins Marcos Jullian Barreto, Batista Avner Marcos Alves, Brito Yuri Neyson Ferreira, Soares Pedro Marcos Gomes, Martins Conceição da Silva, Ribeiro Ronaldo de Albuquerque, Brito Gerly Anne de Castro, de Freitas Marcos Rabelo

机构信息

Department of Surgery, Medical School, Federal University of Ceará, Fortaleza, Brazil.

出版信息

ORL J Otorhinolaryngol Relat Spec. 2017;79(6):336-346. doi: 10.1159/000485514. Epub 2018 Jan 17.

DOI:10.1159/000485514
PMID:29339643
Abstract

BACKGROUND/AIMS: Cisplatin is a chemotherapeutic agent. The use of remote ischemic preconditioning (RIPC) was proposed after the observation that ischemic preconditioning of a cardiac vascular area could protect another completely distinctly.

METHODS

This is an experimental study. Male Wistar rats were anesthetized, and they underwent a hearing evaluation via measurement of the brainstem auditory evoked potential (BSAEP). Then, cisplatin was administered intraperitoneally (IP) at a dose of 8 mg/kg/day for 4 consecutive days to group 1, whereas saline solution was administered IP to group 2. In groups 3 and 4, ischemia of the right hind paw was performed for 10 min, followed by reperfusion for 30 min, after which cisplatin or saline was administered IP to group 3 or group 4, respectively. Afterwards, all animals were evaluated via the BSAEP. The right cochlea was dissected for immunohistochemistry.

RESULTS

RIPC lowered the increase in BSAEP of the animals treated with cisplatin (p = 0.0146). Weight loss decreased in the animals subjected to RIPC (p < 0.005). In group 3, RIPC reversed immunostaining for tumor necrosis factor-α and inducible nitric oxide synthase in the stria vascularis injured by cisplatin (p < 0.05).

CONCLUSION

RIPC protects against systemic toxicity and ototoxicity induced by cisplatin in rats.

摘要

背景/目的:顺铂是一种化疗药物。在观察到心脏血管区域的缺血预处理可以对另一个完全不同的区域产生保护作用后,人们提出了使用远程缺血预处理(RIPC)的方法。

方法

这是一项实验研究。将雄性Wistar大鼠麻醉,通过测量脑干听觉诱发电位(BSAEP)对其进行听力评估。然后,第1组大鼠连续4天腹腔注射(IP)8mg/kg/天的顺铂,而第2组大鼠腹腔注射生理盐水。在第3组和第4组中,对右后爪进行10分钟的缺血,随后再灌注30分钟,之后分别对第3组和第4组大鼠腹腔注射顺铂或生理盐水。之后,通过BSAEP对所有动物进行评估。解剖右耳蜗进行免疫组织化学分析。

结果

RIPC降低了顺铂处理动物的BSAEP升高(p = 0.0146)。接受RIPC处理的动物体重减轻减少(p < 0.005)。在第3组中,RIPC逆转了顺铂损伤的血管纹中肿瘤坏死因子-α和诱导型一氧化氮合酶的免疫染色(p < 0.05)。

结论

RIPC可保护大鼠免受顺铂诱导的全身毒性和耳毒性。

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